To see the other types of publications on this topic, follow the link: Cancer nanotechnology.
Dissertations / Theses on the topic 'Cancer nanotechnology'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 dissertations / theses for your research on the topic 'Cancer nanotechnology.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Ullal, Adeeti (Adeeti Vedantham). "Micro and nanotechnology for cancer treatment." Thesis, Massachusetts Institute of Technology, 2013. http://hdl.handle.net/1721.1/83968.
Full textAbstract:
Thesis (Ph. D. in Biomedical Engineering)--Harvard-MIT Program in Health Sciences and Technology, 2013.Cataloged from PDF version of thesis.
Includes bibliographical references (pages 92-101).
Cancer is responsible for over 7.6 million deaths worldwide; the majority of patients fail to respond to drugs or become resistant over time. In order to gain a better understanding of drug efficacy in patients, we developed three diagnostic technologies to address limitations in sample acquisition and improve the scale and sensitivity of current cancer diagnostic tools. In the first section, we describe a hybrid magnetic and size sorting microfluidic device that isolates rare circulating tumor cells from peripheral blood. The self-assembled magnetic sorter creates strong magnetic fields and effectively removes leukocytes tagged with magnetic nanoparticles. The size sorting region retains the remaining cells in single cell capture sites, while allowing small red blood cells to pass through 5pm gaps. The device achieves over 103 enrichment, up to 96% recovery of cancer cells and allows for on-chip molecular profiling. In the second section we use a magnetic nanoparticle decorated with small molecule drugs to assay target expression and drug binding in mock clinical samples of cancer cells spiked into whole blood. Specifically, we modify a PARP inhibitor (Olabarib) and conjugate it to a dextran coated iron oxide nanoparticle. We measure the presence of the drug nanosensor based on the change in T2 relaxation time using a miniaturized, handheld NMR sensor for point-of-care diagnosis. In the final section, we detail a photocleavable DNA barcoding method for understanding treatment response via multiplexed profiling of cancer cells. We validate our method with a 94 marker panel on different cell lines with varying treatments, showing high correlations to gold standard methods such as immunofluorescence and flow cytometry. Furthermore, we demonstrate single cell sensitivity, and identify a number of expected biomarkers in response to cell treatments. Finally, we demonstrate the potential of our method to help in clinical monitoring of patients by examining intra- and inter-patient heterogeneity, and by correlating pre and post-treatment tumor profiles to patient response. Together, we show how these technologies can help overcome clinical limitations and expedite advancements in cancer treatment.
by Adeeti Ullal
Ph.D.in Biomedical Engineering
2
Mancini, Michael C. "Biomedical instrumentation and nanotechnology for image-guided cancer surgery." Diss., Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/43657.
Full textAbstract:
Once diagnosed, cancer is treated by surgical resection, chemotherapy, radiation therapy, or a combination of these therapies. It is intuitive that physically and completely removing a solid tumor would be an effective treatment. A complete resection of the tumor mass, defined by surgical margins that are clear of neoplasia, is prognostic for a decreased chance of cancer recurrence and an increased survival rate. In practice, complete resection is difficult. A surgeon primarily has only their senses of touch and sight to provide "real-time" guidance in the removal of a tumor while in the operating room. Preoperative imaging can guide a surgeon to a tumor but does not give a continuous update of surgical progress. Intraoperative pathology is limited to a few slides worth of samples: a product of its time-consuming nature and the limited time a patient can remain under general anesthesia. Technologies to guide a surgeon in effecting complete resection of a tumor mass during the surgical procedure would greatly increase cancer survival rates by lowering rates of cancer recurrence; such a technology would also reduce the need for follow-up chemotherapy or radiation therapy. Here, we describe a prototype instrumentation system that can provide intraoperative guidance with exogenous optical contrast agents. The instrumentation combines interactive point excitation, local spectroscopy, and widefield fluorescence imaging to enable low-cost surgical guidance using FDA-approved fluorescent dyes, semiconductor quantum dots (QDs), or surface-enhanced Raman scattering (SERS) nanoparticles. The utility of this surgical system is demonstrated in rodent tumor models using an FDA-approved fluorescent dye, indocyanine green (ICG), and is then more extensively demonstrated with a pre-clinical study of spontaneous tumors in companion canines. The pre-clinical studies show a high sensitivity in detecting a variety of canine tumors with a low false positive rate, as verified by pathology.
We also present a fundamental study on the behavior of quantum dots. QDs are a promising fluorophore for biological applications, including as a surgical contrast agent. To use QDs for in vivo human imaging, toxicity concerns must be addressed first. Although it is suspected that QDs may be toxic to an organism based on the heavy-metal elemental composition of QDs, overt organism toxicity is not seen in long-term animal model studies. We have found that some reactive oxygen species (ROS) generated by the host inflammatory response can rapidly degrade QDs; in the case of hypochlorous acid, optical changes to the QDs are suggestive of degradation occurring within seconds. It is well-known that QDs are sequestered by the immune system when used in vivo---we therefore believe that QD degradation through an inflammatory response may represent a realizable in vivo mechanism for QD degradation. We demonstrate in an in vitro cell culture model that immune cells can degrade QDs through ROS exposure. Knowledge of the degradative processes that QDs would be subject to when used in vivo informs on adaptations that can be made to the QDs to resist degradation. Such adaptations will be important in developing QD-based contrast agents for image guided surgery.
3
Fisher, Jessica Won Hee. "Effective Cancer Therapy Design Through the Integration of Nanotechnology." Thesis, Virginia Tech, 2008. http://hdl.handle.net/10919/34386.
Full textAbstract:
Laser therapies can provide a minimally invasive treatment alternative to surgical resection of tumors. However, therapy effectiveness is limited due to nonspecific heating of target tissue, leading to healthy tissue injury and extended treatment durations. These therapies can be further compromised due to heat shock protein (HSP) induction in tumor regions where non-lethal temperature elevation occurs, thereby imparting enhanced tumor cell viability and resistance to subsequent therapy treatments. Introducing nanoparticles (NPs), such as multi-walled nanotubes (MWNTs) or carbon nanohorns (CNHs), into target tissue prior to laser irradiation increases heating selectivity permitting more precise thermal energy delivery to the tumor region and enhances thermal deposition thereby increasing tumor injury and reducing HSP expression induction. This research investigates the impact of MWNTs and CNHs in untreated and laser-irradiated monolayer cell culture, tissue phantoms, and/or tumor tissue from both thermal and biological standpoints. Cell viability remained high for all unheated NP-containing samples, demonstrating the non-toxic nature of both the nanoparticle and the alginate phantom. Up-regulation of HSP27, 70 and 90 was witnessed in samples that achieved sub-lethal temperature elevations. Tuning of laser parameters permitted dramatic temperature elevations, decreased cell viability, and limited HSP induction in NP-containing samples compared to those lacking NPs. Preliminary work showed MWNT internalization by cells, which presents imaging and multi-modal therapy options for NT use. The lethal combination of NPs and laser light and NP internalization reveals these particles as being viable options for enhancing the thermal deposition and specificity of hyperthermia treatments to eliminate cancer.Master of Science
4
Kim, Gloria J. "Cancer nanotechnology engineering multifunctional nanostructures for targeting tumor cells and vasculatures /." Diss., Atlanta, Ga. : Georgia Institute of Technology, 2007. http://hdl.handle.net/1853/22610.
Full textAbstract:
Thesis (Ph. D.)--Biomedical Engineering, Georgia Institute of Technology, 2007.Committee Chair: Nie, Shuming; Committee Member: Lyon, L. Andrew; Committee Member: McIntire, Larry V.; Committee Member: Murthy, Niren; Committee Member: Prausnitz, Mark R.
5
Sathe, Tushar R. "Integrated Magnetic and Optical Nanotechnology for Early Cancer Detection and Monitoring." Diss., Georgia Institute of Technology, 2007. http://hdl.handle.net/1853/19868.
Full textAbstract:
Despite significant developments in imaging modalities and therapeutics, cancer mortality rates remain unchanged. Detecting cancer before it has spread to other organs improves patient outcome dramatically. Therefore, greater emphasis must be placed on developing novel technology for early cancer detection and disease monitoring. Nanometer-sized materials have unique optoelectronic and magnetic properties. In particular, semiconductor quantum dots (QD) are a new class of fluorophores that are bright, photostable, and can be simultaneously excited to emit different wavelengths of light. Magnetic iron oxide nanoparticles are another class of unique nanomaterials that exhibit superparamagnetism and are strongly magnetized only in the presence of a magnetic field.
In this dissertation, we describe the integration of semiconductor QDs and magnetic iron oxide nanoparticles and potential applications for (i) early detection of cancer biomarkers through routine screening, and (ii) disease monitoring through the capture and analysis of rare circulating tumor cells. First, we describe the development of integrated magneto-optical beads that can be optically encoded and magnetically separable for isolating low amounts of biomolecules from solution. Second, we demonstrate improved detection sensitivity by combining immunomagnetic beads and highly luminescent nanoparticles in a sandwich assay. Next, we describe integration of magnetic and QD nanotechnology for the selective capture and molecular profiling of rare cells. We demonstrate the ability to spectroscopically determine relative molecular levels of markers to identify invasive cells. As disease monitoring requires the analysis of patient blood samples, we have also studied nanoparticle-cell interactions using QDs to determine nanoparticle behavior in whole blood as a function of surface coatings. We observed that anionic nanoparticles with carboxylic acid groups (-COOH) were strongly associated with leukocytes, but interestingly this association was cell specific. Hydroxyl-modified QDs (QD-OH) suppressed binding and uptake by leukocytes as efficiently as PEG-modified QDs. The integration of nanotechnologies represents a new and exciting approach that has the potential to push the limits of detection sensitivity and permit isolation and profiling of multiple biomarkers from large sample volumes.
6
Drah, Mustafa. "The development of nanotechnology-based detection systems for the diagnosis of breast cancer." University of the Western Cape, 2015. http://hdl.handle.net/11394/5021.
Full textAbstract:
Philosophiae Doctor - PhDBreast cancer is one of the major causes of death in South Africa. About 1 in 29 South African women are at risk of developing this type of cancer in their lifetime. The global incidence of breast cancer also increases annually with over 1 million new cases diagnosed every year. Molecular diagnostic techniques such as qRT-PCR, Fluorescent In Situ Hybridization (FISH), Immunohistochemistry (IHC) and ELISA are used to diagnose breast cancer. Some of these diagnostic techniques make use organic fluorophores as fluorescent reporter molecules. The principle of all these diagnostic techniques is reliant on the detection of molecular biomarkers that are associated with the disease. In most cases these molecular biomarkers are DNA, RNA or proteins that are up-regulated in response to or as a result of the disease. The first aim of this study was therefore to identify membrane proteins that are up-regulated in cancers that can potentially be used as biomarkers for the detection of breast cancer. The second aim of this study was to investigate the application of quantum dots in the development of a molecular diagnostic test that can detect a breast cancer biomarker. The most commonly used method to identify molecular biomarkers for diseases have traditionally been gene expression analysis using technologies such as DNA microarray. These technologies have certain limitations and have therefore not been very successful in identifying useful disease biomarkers. Biomarker II discovery by proteomics can overcome some of these limitations and is potentially a more suitable method to identify molecular biomarkers for breast cancer. In this study proteomics in combination with Stable Isotope Labelling with Amino Acids in Cell Culture SILAC was used to do a comparative analysis of the expression levels of membrane proteins present in a human breast cancer cell line (MCF-7) derived from a breast cancer patient and a human breast cell line (MCF- 12A) derived from a healthy individual. This led to the identification of the transmembrane protein, GFRA1 as potential new biomarker for breast cancer. This study showed that this protein is over expressed in MCF-7 cells as compared to MCF-12A cells and that it is also highly expressed in the myoepthelial cells of the milk ducts of breast cancer patients. This study also demonstrates the use of molecular beacon technology to develop a DNA probe for the detection of cDNA encoding the CK19 gene, which is a known biomarker for breast cancer. In the development of this probe, quantum dots were used as the fluorescence reporter. This molecular beacon probe was able to demonstrate the over expression of CK19 in MCF-7 cells. This study shows that this technology can potentially be used as a diagnostic test for breast cancer and since quantum dots are used in the development of these molecular beacon probes, this diagnostic test can potentially facilitate the development of multiplex detection systems for the diagnosis of breast cancer. Molecular beacon technology can potentially also be used to detect novel biomarkers such as GFRA1.
7
Motala, Ismail Mohammed, and Saartjie Roux. "Formulation of an optimal non-targeted liposome preparation for fusion with tumour cell line membranes." Thesis, Nelson Mandela Metropolitan University, 2016. http://hdl.handle.net/10948/12220.
Full textAbstract:
The most common treatment used for cancer is chemotherapy. Chemotherapeutic agents have a greater affinity for rapidly dividing cells which is a characteristic of tumour cells. Although anti-cancer agents have their advantages in providing anti-cancer effects, they can be seen as highly toxic molecules posing a threat to normal healthy tissue within the human body. However, these toxic therapies need to be delivered to tumour sites without damaging healthy tissue. Liposomes can serve as a delivery system for these toxic molecules and be delivered to the tumour site via the EPR effect. Hence, liposomes that fuse with tumour cell line membranes are advantageous in delivering payloads of drugs directly into the tumour cell without damaging normal healthy tissue. The aim of the study was to formulate an optimised liposome preparation in order to enhance cellular uptake by MCF-7, Caco-2 and C3A cancer cell lines via membrane fusion. The optimal liposome formulation was aimed to be prepared utilising a statistical design approach in order to determine the ranges of the parameters that were furthermost optimal in formulating an ideal liposome preparation. The primary screening design was conducted using a 24-1 fractional factorial design that took into account the four parameters that were used to determine the optimisation of the liposomal preparation. The four variables used in the liposome preparation were the phospholipid type (PS or DOPE), the concentration of cholesteryl hemisuccinate (CHEMS) (10 – 40 %), the concentration of PEG2000-PE (0.5 – 4 %) and liposome size (100 or 200 nm). Liposomes were prepared using thin film hydration method and characterisation for size and zeta potential was carried out using photon correlation spectroscopy (PCS). Visual characterisation of liposome size was carried out using atomic force microscopy (AFM). Liposomes were exposed the cancer cell lines with visualisation and uptake being measured using fluorescent microscopy and flow cytometry, respectively. An optimal liposome preparation was prepared following the statistical design method. The optimal liposome preparation consisted of phospholipid type PS, 22.91 % of CHEMS, 4 % of PEG2000-PE and a liposome size of 200 nm. AFM analysis has shown that optimal liposome sizes ranged between 130 and 170 nm. Flow cytometry analysis indicated high level of liposome uptake with actual values falling below the predicted values set out by the statistical design. Fluorescence microscopy captured images of the fluorescent liposomes concentrated on the membrane of cells. The objective of the study was to determine from literature which variables would be desirable in preparing an optimal non-targeted liposome preparation. This was achieved by identifying four such variables and utilising them in a statistical design approach which was screened in order to determine the ideal parameters in preparing the optimised liposome batch. Therefore, from the results obtained it can be concluded that the aim of the study were met by preparing an optimal liposome preparation that has the ability to fuse with the tumour cell line membranes.
8
Platt, Virginia M. "Surface functionalization of liposomes with proteins and carbohydrates for use in anti-cancer applications." Diss., Search in ProQuest Dissertations & Theses. UC Only, 2010. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3390073.
Full textAbstract:
Thesis (Ph.D.)--University of California, San Francisco with the University of California, Berkeley, 2010.Source: Dissertation Abstracts International, Volume: 71-02, Section: B, page: . Adviser: Francis C. Szoka.
9
Petryk, Alicia Ailie. "Magnetic nanoparticle hyperthermia as an adjuvant cancer therapy with chemotherapy." Thesis, Dartmouth College, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3634608.
Full textAbstract:
Magnetic nanoparticle hyperthermia (mNPH) is an emerging cancer therapy which has shown to be most effective when applied in the adjuvant setting with chemotherapy, radiation or surgery. Although mNPH employs heat as a primary therapeutic modality, conventional heat may not be the only cytotoxic effect. As such, my studies have focused on the mechanism and use of mNPH alone and in conjunction with cisplatinum chemotherapy in murine breast cancer cells and a related in vivo model. MNPH was compared to conventional microwave tumor heating, with results suggesting that mNPH (mNP directly injected into the tumor and immediately activated) and 915 MHz microwave hyperthermia, at the same thermal dose, result in similar tumor regrowth delay kinetics. However, mNPH shows significantly less peri-tumor normal tissue damage. MNPH combined with cisplatinum also demonstrated significant improvements in regrowth delay over either modality applied as a monotherapy. Additional studies demonstrated that a relatively short tumor incubation time prior to AMF exposure (less than 10 minutes) as compared to a 4-hour incubation time, resulted in faster heating rates, but similar regrowth delays when treated to the same thermal dose. The reduction of heating rate correlated well with the observed reduction in mNP concentration in the tumor observed with 4 hour incubation. The ability to effectively deliver cytotoxic mNPs to metastatic tumors is the hope and goal of systemic mNP therapy. However, delivering relevant levels of mNP is proving to be a formidable challenge. To address this issue, I assessed the ability of cisplatinum to simultaneously treat a tumor and improve the uptake of systemically delivered mNPs. Following a cisplatinum pretreatment, systemic mNPs uptake was increased by 3.1 X, in implanted murine breast tumors. Additional in vitro studies showed the necessity of a specific mNP/ Fe architecture and spatial relation for heat-based cytotoxicity in cultured cells.
10
Ahmed, Muneer. "The application of magnetic nanotechnology to the surgical management of non-palpable breast cancer." Thesis, King's College London (University of London), 2015. http://kclpure.kcl.ac.uk/portal/en/theses/the-application-of-magnetic-nanotechnology-to-the-surgical-management-of-nonpalpable-breast-cancer(e18d9196-1462-4302-b95e-aa7f64afc1c7).html.
Full textAbstract:
Background: Breast cancer is the most common cancer in the United Kingdom, with over one-third of all cases diagnosed annually being clinically occult (non-palpable). The current standard of care is surgical wide local excision using wire-guided localization and axillary staging by sentinel node biopsy. Wire-guided localization possesses limitations, which have resulted in alternative localization techniques being developed – although these have failed to gain mainstream acceptance. This thesis examined the current evidence supporting other localization techniques and aimed to develop an alternative, overcoming existing limitations. Materials and methods: This thesis examined a handheld magnetometer and magnetic tracer for localization properties within pre-clinical phantom models, progressing to the development of an in vivo porcine model, which was also used to assess concurrent sentinel lymph node biopsy. This was followed by the establishment of the first, in-man feasibility study of a magnetic tracer for sentinel node and occult lesion localization using an intra-tumoral injection of magnetic tracer for patients with non-palpable breast cancer (MagSNOLL trial, UKCRN 14979). Results: This thesis demonstrated the ability of a magnetic tracer to localise at a specific site within phantom models. This was replicated within an in vivo porcine model in addition to concurrent sentinel lymph node biopsy with a single injection of the magnetic tracer. These findings were translated into a clinical trial (MagSNOLL), which demonstrated that an intra-tumoral injection of magnetic tracer allowed successful lesion localization independently of a wire. Concurrent magnetic sentinel lymph node biopsy was demonstrated to be feasible but inferior to the standard ‘dual technique’ of radioisotope and blue dye. Conclusion: Magnetic lesion localization is feasible without the need for a wire or radioisotopes. Further work to assess the retention of the magnetic tracer in vivo and optimisation of sentinel node identification rates are required.
11
Hayden, Steven C. "Novel applications of nanotechnology in medicine and green energy." Diss., Georgia Institute of Technology, 2012. http://hdl.handle.net/1853/51927.
Full textAbstract:
The development of techniques for colloidal nanoparticle synthesis has allowed scientists to fabricate materials that can manipulate light on a scale that is small even compared to the wavelength of the light itself. This ability has led to the development of myriad and diverse applications of nanostructures in wide-ranging fields. This thesis focuses on the investigation and exploitation of nanoscale material properties in the fields of medicine and energy. The unique optical properties of nanoparticles arise from their size and their high surface area to volume ratios compared to bulk materials. As a result of this relationship, the surface characteristics of nanoparticles generally dominate their properties, whereas in bulk materials the surface atoms have very little bearing on the properties of the composite. Chapter 1 gives an introduction to nanoparticles and their optical properties, including a discussion of the plasmon resonance and the properties imbued upon nanoparticles possesing such a resonance as well as the applicability of these properties that will be explored in the subsequent chapters. Chapter 2 presents a study of the interaction of cationic, hydrophobic gold nanoparticles as probes to elucidate specific regions of interest on cell surfaces. The high imaging contrast of gold nanoparticles in electron microscopy allows for visual, macroscopic observation of the aggregation patterns formed by these nanoparticles on cell surfaces. Plasmon resonant coupling between proximal nanoparticles is exploited in order to monitor nanoprobe binding and localization over time with the use of extinction spectroscopy. The role of surface proteins in the nanoparticle-cell surface interaction is elucidated, generating composite data with relevance in pharmaceutical development and pharmacokinetics. Additionally, bacteria strain-dependent toxicity is observed and subsequently investigated for smaller gold nanoparticle probes, demonstrating a potential use for nanoparticles as strain-specific antibiotics. The development of affordable, effective antibiotic technology is one of the major scientific challenges of our time; infections from pathogen-infested drinking water alone account for millions of deaths each year worldwide. In Chapter 3, we investigate the use of titanium dioxide as an inexpensive method to harness solar energy to split water into reactive species and thereby decontamitate solutions of E. coli. Though titanium dioxide is an excellent catalyst for water splitting, it requires UV irradiation, which is fairly lacking in the solar emission spectrum. Further, recuperation of titanium dioxide nanoparticles from solution is non-trivial, and its immobilization into a film greatly limits its surface area and charge carrier efficiency, thereby limiting its activity. We treat both the poor visible light absorption capability as well as the surface area limitation in this study. CdS semiconductor nanocrystals are used to extend the absorption edge of TiO₂ further into the visible light region of the spectrum by providing for lower-energy photon absorption and charge injection into titanium dioxide. TiO₂ is also electrochemically anodized to generate TiO₂ nanotube arrays, which have greatly increased surface area as well as more efficient charge transfer properties compared to thin films of TiO₂ nanoparticles. The utility of nanoparticles in increasing the light absorption of other systems continues as a theme in the work presented in the next two chapters. Chapter 4 ex- amines the plasmonic enhancement of the solar energy conversion in a biomimetic system. In this endeavor, we enhance the photocurrent generated by a light-transducing, proton-pumping protein, bacteriorhodopsin, in a 3-dimensional wet electrochemical cell. First, we increase the overall charge carrier separation with the use of a proton- selective membrane in order to minimize ionic depolarization in the cell. We then use plasmonic nanoparticles to exploit an irregularity in the bacteriorhodopsin photocycle known as the blue light effect. This effect shortens the timescale of the photocyle by more than 99% via blue photon absorption, but it has a very low natural occurrence. Plasmonic nanoparticles tuned to the blue wavelength region increase the flux of blue photons on a local level and thereby increase the overall photocurrent generation. We first examine the importance of nanoparticle field strength to photocurrent enhancement using silver nanospheres with different capping shell thicknesses. We then consider the trade-off between (1) using a nanoparticle with a plasmon resonance tuned perfectly to the blue wavelength region and (2) using a nanoparticle with a stronger field intensity but weaker energetic presence in the blue. By minimizing ionic depolarization, minimizing shielding of the plasmon electromagnetic field, and maximizing the field strength while maintaining the plasmon frequency at the proper wavelength, we demonstrate an enhancement of 5,000-fold in the photocurrent production by bacteriorhodopsin. Chapter 5 explores a variation on the theme of Chapter 4 with an application in cancer therapeutics. Here, a photodynamic cancer drug, protoporphyrin IX (PpIX), is incorporated into complexes with silver nanospheres, gold nanospheres, and gold nanorods. Each of these nanoparticles displays a plasmon resonance in a different region of the spectrum, with consequent different overlap with the absorption or emission of the drug. Photodynamic therapeutic potential is measured in situ and in vivo, and the drug activity is shown to be strongest when drug absorption overlaps with plasmon resonance. Absorption by electronic excitations in the particle crystal lattice is shown to function as a competitive light filter and decrease drug activity. Additionally, the method of attachment of the drug to the nanoparticle is examined. Maximum enhancement of drug activity is shown to require the drug to remain bound close to the nanoparticle surface, where the electromagnetic field strength is highest. This plasmonic enhancement effect on drug activity is shown to outstrip the increase in drug activity seen when using the nanoparticle solely as a delivery platform. In Chapter 6, some synthetic techniques are presented for various nanomaterials. Included are syntheses for gold, silver, and semiconductor nanoparticles of a variety of shapes and sizes as well as for TiO₂ nanotube arrays. The relationship of the ratio of capping agent to metal salt is explored for gold nanospheres, and a method for facile tuning of the longitudinal plasmon resonance displayed by gold nanorods is presented. Synthetic techniques are also presented for the nanoparticles whose applications are explored in the preceding chapters.
12
Lei, Tingjun. "Multifunctional Nanoparticles in Cancer: in vitro Characterization, in vivo Distribution." FIU Digital Commons, 2013. http://digitalcommons.fiu.edu/etd/872.
Full textAbstract:
A novel biocompatible and biodegradable polymer, termed poly(Glycerol malate co-dodecanedioate) (PGMD), was prepared by thermal condensation method and used for fabrication of nanoparticles (NPs). PGMD NPs were prepared using the single oil emulsion technique and loaded with an imaging/hyperthermia agent (IR820) and a chemotherapeutic agent (doxorubicin, DOX). The size of the void PGMD NPs, IR820-PGMD NPs and DOX-IR820-PGMD NPs were approximately 90 nm, 110 nm, and 125 nm respectively. An acidic environment (pH=5.0) induced higher DOX and IR820 release compared to pH=7.4. DOX release was also enhanced by exposure to laser, which increased the temperature to 42°C. Cytotoxicity of DOX-IR820-PGMD NPs was comparable in MES-SA but was higher in Dx5 cells compared to free DOX plus IR820 (pIn vivomouse studies showed that NP formulation significantly improved the plasma half-life of IR820 after tail vein injection. Significant lower IR820 content was observed in kidney in DOX-IR820-PGMD NP treatment as compared to free IR820 treatment in our biodistribution studies (p
13
Whitney, Jon R. "Single Walled Carbon Nanohorns as Photothermal Absorbers, and Incorporation of Spatial Digital Image Analysis into Cancer Diagnostics and Therapy." Diss., Virginia Tech, 2013. http://hdl.handle.net/10919/50616.
Full textAbstract:
�Background: Photothermal therapy is an actively researched cancer treatment alternative to chemotherapy and resection due to its potential as a minimally invasive treatment with fewer health complications than high energy radiation therapies. �The effectiveness of photothermal therapy may be enhanced with the use of photoabsorbtive nanoparticles by increasing heat generation and improving spatial selectivity. �While photothermal therapy is a spatially distributed treatment, traditional experimental analysis methods used to assess photothermal therapy have either lacked spatial assessment such as is the case with standard viability assays of cell monolayers, or they only provide macroscopic treatment information, such as the measurement of the diameters of implanted mice flank tumors post-treatment. �Goals: �This work aims to accomplish two major goals. �The first is to determine the therapeutic impact of combining Single Walled Carbon Nanohorns (SWNHs) with photothermal therapy. �The second is to advance the measurement tools used to assess photothermal therapy by developing viability measurement methods which incorporate detailed quantitative spatial information
Methods: Photothermal therapy was tested with and without SWNHs in in vitro cell monolayers, in vitro tissue phantoms, and ex-vivo tissue. �Digital image analysis methods were developed which allowed for the use of viability assays and histological information to be identified and organized spatially. �These methods were then used to compare the impact of cellular microenvironment and heating method on Arrhenius parameters.
Results: The inclusion of SWNHs dramatically increased the temperatures reached in each experiment. �Digital image analysis methods were shown to quantify spatial viability with a high degree of accuracy and precision in 2D and 3D. �Experimental data indicated that there were areas of collateral damage (partially treated tissue) surrounding areas of completely treated tissue ranging which were between 46% and 78% of the completely treated volume. �In each case the heat transfer properties of the experimental system had a large impact on the area of treatment. �Variation in the temperature and viability response of photothermal therapy for specific laser and nanoparticle treatment parameters was quantified. �
����Conclusions: This research has brought an experimental cancer treatment procedure from experiments in cell monolayers to tests in ex-vivo tissue to analyze viability response. �The strengths of photothermal therapy such as its minimally invasive nature, and effectiveness at killing cells were experimentally demonstrated. � �This research has also developed the tools necessary to assess the spatial impact in vitro and lay the foundations for assessing spatial impact in vivo. �These tools may be used to assess other treatments beyond photothermal therapy, and serve as a basis for improving the analysis of biological systems both in vitro and in vivo.
Ph. D.
14
Babahosseini, Hesam. "Single Cell Biomechanical Phenotyping using Microfluidics and Nanotechnology." Diss., Virginia Tech, 2016. http://hdl.handle.net/10919/64502.
Full textAbstract:
Cancer progression is accompanied with alterations in the cell biomechanical phenotype, including changes in cell structure, morphology, and responses to microenvironmental stress. These alterations result in an increased deformability of transformed cells and reduced resistance to mechanical stimuli, enabling motility and invasion. Therefore, single cell biomechanical properties could be served as a powerful label-free biomarker for effective characterization and early detection of single cancer cells. Advances and innovations in microsystems and nanotechnology have facilitated interrogation of the biomechanical properties of single cells to predict their tumorigenicity, metastatic potential, and health state.
This dissertation utilized Atomic Force Microscopy (AFM) for the cell biomechanical phenotyping for cancer diagnosis and early detection, efficacy screening of potential chemotherapeutic agents, and also cancer stem-like/tumor initiating cells (CSC/TICs) characterization as the critical topics received intensive attention in the search for effective cancer treatment. Our findings demonstrated the capability of exogenous sphingosine to revert the aberrant biomechanics of aggressive cells and showed a unique, mechanically homogeneous, and extremely soft characteristic of CSC/TICs, suitable for their targeted isolation. To make full use of cell biomechanical cues, this dissertation also considered the application of nonlinear viscoelastic models such as Fractional Zener and Generalized Maxwell models for the naturally complex, heterogeneous, and nonlinear structure of living cells.
The emerging need for a high-throughput clinically relevant alternative for evaluating biomechanics of individual cells led us to the development of a microfluidic system. Therefore, a high-throughput, label-free, automated microfluidic chip was developed to investigate the biophysical (biomechanical-bioelectrical) markers of normal and malignant cells.
Most importantly, this dissertation also explored the biomechanical response of cells upon a dynamic loading instead of a typical transient stress. Notably, metastatic and non-metastatic cells subjected to a pulsed stress regimen exerted by AFM exhibited distinct biomechanical responses. While non-metastatic cells showed an increase in their resistance against deformation and resulted in strain-stiffening behavior, metastatic cells responded by losing their resistance and yielded slight strain-softening. Ultimately, a second generation microfluidic chip called an iterative mechanical characteristics (iMECH) analyzer consisting of a series of constriction channels for simulating the dynamic stress paradigm was developed which could reproduce the same stiffening/softening trends of non-metastatic and metastatic cells, respectively. Therefore, for the first time, the use of dynamic loading paradigm to evaluate cell biomechanical responses was used as a new signature to predict malignancy or normalcy at a single-cell level with a high (~95%) confidence level.Ph. D.
15
He, Felicia Jane. "Targeting Metastatic Breast Cancer Using Dual-Ligand Nanoparticles." Case Western Reserve University School of Graduate Studies / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=case1499699087340348.
Full text
16
Guo, Sijin. "RNA Nanoparticle as A Safe and Effective Drug Delivery Platform for Cancer Therapy." The Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1561719043509709.
Full text
17
Murray, Abner A. "Plant Virus Nanoparticle In Situ Cancer Immunotherapies." Case Western Reserve University School of Graduate Studies / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=case1532370850718292.
Full text
18
Meyer, Miché Desline. "Peptide functionalised gold nanorods for the selective eradication of target cells using photothermal therapy." University of the Western Cape, 2019. http://hdl.handle.net/11394/6771.
Full textAbstract:
>Magister Scientiae - MScCancer is one of the leading causes of death, worldwide. Mortality tolls are estimated to reach approximately 13.1 million in 2030. These statistics suggest that current therapeutic strategies are not effective. This is partly due to the fact that the drugs used in the treatment of cancer lack selectivity and specificity, which lead to undesirable side effects and reduced drug efficacy. There is therefore a need for alternative therapeutic approaches. In view of this, the therapeutic goal of chemotherapy has shifted towards targeted drug delivery systems, which have been successfully demonstrated using nanotechnology. The nano-based drug delivery vehicles that specifically target diseased cells are appealing as they could reduce drug toxicity towards healthy tissues and be more effective at lower dosages. The main aim of this study was to develop gold nanorods (AuNRs) capable of inducing cell death in cancer cells specifically. Selectivity of the AuNRs (denoted as AGK) for cancer cells was achieved by conjugating the AuNRs to a peptide (Adipose Homing Peptide or AHP) that has high affinity and specificity for a cell surface receptor (prohibitin or PHB) that is expressed on some cancer cells. Cell death was achieved through conjugating the AuNRs to a pro-apoptotic peptide, D(KLAKLAK)2. Spherical AuNPs (AuNSs) conjugated with AHP and D(KLAKLAK)2, capable of selectively inducing apoptosis in cancer cells that express PHB, was previously reported. However, in this study the AuNSs were replaced with AuNRs. AuNRs has the ability to absorb light in the near infrared (NIR) light spectrum and converts this light energy into heat. This property of AuNRs has been used in several studies to demonstrate the application of AuNRs for the treatment of cancer using photothermal therapy (PTT). Consequently, the AuNRs described in this study can also be used for PTT. These AuNRs can induce cell death through the target specific delivery of the pro-apoptotic peptide D(KLAKLAK)2 as well as through PTT. The study showed that three human cancer cell lines (PC-3, Caco-2 and U-87) express PHB. The cytotoxicity testing of AGK AuNPs on PC-3 cells showed that these AuNRs could induce apoptosis in these cells without exposure to a NIR light source. The study also shows that AuNRs conjugated with the targeting peptide only (denoted as AG) can induce cell death in Caco-2 through PTT. This study demonstrates the potential of the AuNRs described in this study for application in the targeted elimination of cancer cells through the selective induction of PTT and apoptosis.
19
Langsner, Robert James. "Optical contrast agents to visualize molecular expression in breast cancer." Thesis, Rice University, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3577602.
Full text
20
Nemati, Porshokouh Zohreh. "Novel Magnetic Nanostructures for Enhanced Magnetic Hyperthermia Cancer Therapy." Scholar Commons, 2016. http://scholarcommons.usf.edu/etd/6548.
Full textAbstract:
In this dissertation, I present the results of a systematic study on novel multifunctional nanostructure systems for magnetic hyperthermia applications. All the samples have been synthesized, structurally/magnetically characterized, and tested for magnetic hyperthermia treatment at the Functional Materials Laboratory of the University South Florida. This work includes studies on four different systems: (i) Core/shell Fe/γ-Fe2O3 nanoparticles; (ii) Spherical and cubic exchange coupled FeO/Fe3O4 nanoparticles; (iii) Fe3O4 nano-octopods with different sizes; (iv) High aspect ratio FeCo nanowires and Fe3O4 nanorods.
In particular, we demonstrated the enhancement of the heating efficiency of these nanostructures by creating monodisperse and highly crystalline nanoparticles, and tuning their magnetic properties, mainly their saturation magnetization (MS) and effective anisotropy, in controlled ways. In addition, we studied the influence of other parameters, such as the size and concentration of the nanoparticles, the magnitude of the applied AC magnetic field, or different media (agar vs. water), on the final heating efficiency of these nanoparticles.
For the core/shell Fe/γ-Fe2O3 nanoparticles, a modest heating efficiency has been obtained, resulting mainly from the strong reduction in MS caused by the shrinkage of the core with time. However, for sizes above 14 nm, the shrinkage process is much slower and the obtained heating efficiency is better than the one exhibited by conventional solid nanoparticles of the same size.
In the case of the exchange-coupled FeO/Fe3O4 nanoparticles, we successfully created two sets of comparable particles: spheres with 1.5 times larger MS than the cubes, and cubes with 1.5 times larger effective anisotropy than the spheres, while keeping the other parameters the same. Our results show that increasing the effective anisotropy of the nanoparticles gives rise to a greater heating efficiency than increasing their MS.
The Fe3O4 nano-octopods, with enhanced surface anisotropy, present better heating efficiency than their spherical and cubic nanoparticles, especially in the high field region, and we have shown that by tuning their size and the effective anisotropy, we can optimize their heating response to the applied AC magnetic field. For magnetic fields, smaller than 300−400 Oe we found that the smallest nano-octopods give the best heating efficiency. Yet if we increase the AC field value, the bigger octopods show an increased heating efficiency and become more effective.
Finally, the FeCo nanowires and Fe3O4 nanorods exhibit enhanced heating efficiency with increasing aspect ratio when aligned in the direction of the applied AC magnetic field, due to the combined effect of shape anisotropy and dipolar interactions. Of all the studied systems, these 1D high aspect ratio nanostructures have displayed the highest heating rates.
All of these findings point toward an important fact that tuning the structural and magnetic parameters in general, and the effective anisotropy in particular, of the nanoparticles is a very promising approach for improving the heating efficiency of magnetic nanostructures for enhanced hyperthermia.
21
Leonard, Marissa. "Overcoming Breast Cancer Metastasis with Novel RNA Aptamers." University of Cincinnati / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1572879601351414.
Full text
22
Bagley, Alexander Francis. "Optically-Active Nanomaterials for Diagnostic and Therapeutic Applications in Ovarian Cancer." Thesis, Harvard University, 2014. http://dissertations.umi.com/gsas.harvard:11517.
Full textAbstract:
The clinical management of cancer has principally relied upon surgery, radiation therapy, and chemotherapy for many decades. Despite recent advances in molecularly-targeted diagnostic and therapeutic agents, the long-term survival rates in patients with solid malignancies including ovarian cancer have improved only incrementally. Nanotechnologies designed to locally interrogate and modulate the tumor microenvironment offer a promising opportunity to enhance existing treatment modalities and establish new therapeutic paradigms. By virtue of their elemental composition, geometry, and surface chemistry, nanomaterials can be engineered with optical and pharmacokinetic properties which permit these agents to localize, fluoresce, and deposit energy within tumors. Nanomaterials therefore provide a clear route towards future approaches for sensitive diagnosis and imaging of tumors and targeted therapeutic delivery.
23
To, Yuk-fai, and 杜鈺輝. "Potential biomedical application of metallic nanoparticles." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B39634322.
Full text
24
Binzel, Daniel W. "Thermodynamics and Kinetics of the Three-Way Junction of Phi29 Motor pRNA and its Assembly into Nanoparticles for Therapeutic Delivery to Prostate Cancer." UKnowledge, 2016. http://uknowledge.uky.edu/pharmacy_etds/53.
Full textAbstract:
The emerging field of RNA nanotechnology necessitates creation of functional RNA nanoparticles, but has been limited by particle instability. Previously, it was found the three-way junction (3WJ) of the Phi29 DNA packaging motor pRNA was found to be ultra-stable and assemble in solution without the presence of metal ions. The three-way junction is composed of three short oligo RNA strands and proven to be thermodynamically stable. Here the assembly mechanism, thermodynamic and enzymatic stabilities, and kinetics are examined in order to understand the stability behind this unique motif. Thermodynamic and kinetics studies found that the pRNA 3WJ formed out of three components at a rapid rate creating a single-step three component collision with a lack of dimer intermediate formation while being governed by entropy, instead of the commonly seen enthalpy. Furthermore, the pRNA 3WJ proved to be stable at temperatures above 50 °C, concentrations below 100 pM, and produced a free energy of formation well below other studied RNA structures and motifs. With the high stability and folding efficiency of the pRNA 3WJ, it serves as an ideal platform for multi-branched RNA nanoparticles constructed through bottom-up techniques. RNA nanoparticles were constructed for the specific targeting of prostate cancer cells expressing Prostate Specific Membrane Antigen (PSMA) by receptor mediated endocytosis through the addition of an RNA aptamer; and the delivery of anti-miRNA sequences for gene regulation. The resulting nanoparticles remained stable while showing highly specific binding and entry in PSMA positive cells through cell surface receptor endocytosis. Furthermore, the entry of the nanoparticles allowed for the knockdown of against onco-miRNAs. Nanoparticles harboring antimiRNAs led to the upregulation of tumor suppressor genes, and signaling of apoptotic pathways. These findings display RNA nanotechnology can result in the production of stable nanoparticles and result in the specific treatment of cancers, specifically prostate cancer.
25
Confeld, Matthew Ian. "A Nano-Sized Approach to Exploiting the Pancreatic Tumor Microenvironment." Diss., North Dakota State University, 2019. https://hdl.handle.net/10365/31354.
Full text
26
Mbandezi, Yamkela. "Evaluation of cytotoxic activity of gold nanoparticles naturally synthesised from South African indigenous medicinal plant extracts." University of the Western Cape, 2018. http://hdl.handle.net/11394/6786.
Full textAbstract:
>Magister Scientiae - MScNanotechnology has emerged as a promising field in the quest to address health conditions. Green nanotechnology is a fairly new branch of nanotechnology, which aims to produce and utilize nanomaterials in a way that is safe for living organisms and their environment. Plant extracts are increasingly used in the green synthesis of gold nanoparticles (AuNPs), which involves the reduction of sodium tetrachloroaurate (III) dehydrate by phytochemicals present in the plant extract. It is probable that the green synthesised AuNPs are more biocompatible than chemically synthesised AuNPs as biomolecules of plant origin are involved in the synthesis process. Therefore, this study aimed to explore various water extracts from indigenous South African plants, which included Perlagonium capitatum, Otholobium bracteolatum, Gerbera linnae, Morrella quercifolia, Searsia lucida, Phylica bubescens, Euclea racemosa, Tetragonia fruticosa, and Searsia glauca for their potential to synthesize AuNPs and to investigate their toxicity towards several microorganisms known to cause skin infections. These organisms play a significant role in delaying the healing of wounds. The antimicrobial properties of nanoparticles are increasing exploited in the production of wound treatments.
27
González, Pedroza María Guadalupe 629035, and Pedroza María Guadalupe González. "Biosíntesis, caracterización y evaluación de la respuesta antiproliferativa de nanopartículas de plata, obtenidas a base de extractos de annona muricata, sobre líneas celulares de cáncer de mama." Tesis de doctorado, Universidad Autónoma del Estado de México, 2020. http://hdl.handle.net/20.500.11799/105566.
Full textAbstract:
ABSTRACT Currently treatments for breast cancer are expensive and not very accessible, due to this, it requires the development of new routes of administration, treatments and novel materials, such as the one proposed. Carrying out the biosynthesis of silver nanoparticles (AgNPs) using extracts of a plant well known for its anticancer activity known as "Soursop" (Annona muricata); where the main active compounds of A. muricata (in leaves, stems and husk) are acetogenins and polyphenols, among others, which means that they can be used as reducing agents; It should be noted that anticancer activity is directly attributed to acetogenins. The biosynthesized AgNPs with leaf extract (AgNPs-EH) and with shell extract (AgNPs-EC) of A. muricata; were characterized by means of the UV-Vis technique, to observe the optical properties of the AgNPs, comparing the reaction times against the growth of the optical response known as Surface Plasmonic Resonance (RPS), as well as Transmission Electron Microscopy (TEM), to recognize the morphology and the average sizes of nanoparticle, with the help of the Scanning Electron Microscopy (SEM), a chemical mapping was achieved, to observe the distribution of the AgNPs in the medium, as well as with the help of the EDS technique (Energy-dispersive X-ray spectroscopy) the elemental chemical composition of the AgNPs was identified. In addition, by means of FT-IR it was possible to identify the vibrational mode of the functional groups present in the extracts. Achieving elucidate the cell viability of AgNPs in cell lines such as MCF-7, MDA-MB-468 and macrophages
28
Hondroulis, Evangelia. "Real-time Biosensor for the Assessment of Nanotoxicity and Cancer Electrotherapy." FIU Digital Commons, 2013. http://digitalcommons.fiu.edu/etd/972.
Full textAbstract:
Knowledge of cell electronics has led to their integration to medicine either by physically interfacing electronic devices with biological systems or by using electronics for both detection and characterization of biological materials. In this dissertation, an electrical impedance sensor (EIS) was used to measure the electrode surface impedance changes from cell samples of human and environmental toxicity of nanoscale materials in 2D and 3D cell culture models. The impedimetric response of human lung fibroblasts and rainbow trout gill epithelial cells when exposed to various nanomaterials was tested to determine their kinetic effects towards the cells and to demonstrate the biosensor’s ability to monitor nanotoxicity in real-time. Further, the EIS allowed rapid, real-time and multi-sample analysis creating a versatile, noninvasive tool that is able to provide quantitative information with respect to alteration in cellular function.
We then extended the application of the unique capabilities of the EIS to do real-time analysis of cancer cell response to externally applied alternating electric fields at different intermediate frequencies and low-intensity. Decreases in the growth profiles of the ovarian and breast cancer cells were observed with the application of 200 and 100 kHz, respectively, indicating specific inhibitory effects on dividing cells in culture in contrast to the non-cancerous HUVECs and mammary epithelial cells. We then sought to enhance the effects of the electric field by altering the cancer cell’s electronegative membrane properties with HER2 antibody functionalized nanoparticles. An Annexin V/EthD-III assay and zeta potential were performed to determine the cell death mechanism indicating apoptosis and a decrease in zeta potential with the incorporation of the nanoparticles. With more negatively charged HER2-AuNPs attached to the cancer cell membrane, the decrease in membrane potential would thus leave the cells more vulnerable to the detrimental effects of the applied electric field due to the decrease in surface charge. Therefore, by altering the cell membrane potential, one could possibly control the fate of the cell. This whole cell-based biosensor will enhance our understanding of the responsiveness of cancer cells to electric field therapy and demonstrate potential therapeutic opportunities for electric field therapy in the treatment of cancer.
29
Rodzinski, Alexandra. "Targeted and Controlled Anticancer Drug Delivery and Release with Magnetoelectric Nanoparticles." FIU Digital Commons, 2016. http://digitalcommons.fiu.edu/etd/2976.
Full textAbstract:
A major challenge of cancer treatment is successful discrimination of cancer cells from healthy cells. Nanotechnology offers multiple venues for efficient cancer targeting. Magnetoelectric nanoparticles (MENs) are a novel, multifaceted, physics-based cancer treatment platform that enables high specificity cancer targeting and externally controlled loaded drug release. The unique magnetoelectric coupling of MENs allows them to convert externally applied magnetic fields into intrinsic electric signals, which allows MENs to both be drawn magnetically towards the cancer site and to electrically interface with cancer cells. Once internalized, the MEN payload release can be externally triggered with a magnetic field. MENs uniquely allow for discrete manipulation of the drug delivery and drug release mechanisms to allow an unprecedented level of control in cancer targeting. In this study, we demonstrate the physics behind the MEN drug delivery platform, test the MEN drug delivery platform for the first time in a humanized mouse model of cancer, and characterize the biodistribution and clearance of MENs. We found that MENs were able to fully cure the model cancer, which in this case was human ovarian carcinoma treated with paclitaxel. When compared to conventional magnetic nanoparticles and FDA approved organic PLGA nanoparticles, MENs are the highest performing treatment, even in the absence of peripheral active targeting molecules. We also mapped the movement through peripheral organs and established clearance trends of the MENs. The MENs cancer treatment platform has immense potential for future medicine, as it is generalizable, personalizable, and readily traceable in the context of treating essentially any type of cancer.
30
Zhao, Xiaobin. "Targeting CD37 and folate receptor for cancer therapy strategies based on engineered protein and liposomes /." Columbus, Ohio : Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1174678307.
Full text
31
Pan, Tao. "Towards early stage disease detection in microdevices : fabrication and testing of micro total analysis systems for bioanalytical applications / /." Diss., CLICK HERE for online access, 2007. http://contentdm.lib.byu.edu/ETD/image/etd1836.pdf.
Full text
32
Zhang, Yu. "Photothermal effect of PS coated Fe3O4 nanoparticles via near-infrared laser and effect of mimic body tissue depth on hyperthermic ablation of MDA-MB-231." University of Cincinnati / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1445343075.
Full text
33
N'diaye, Marline. "Formulation de liponanoparticules pour le traitement du rétinoblastome par bithérapie chimio/photodynamique." Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS572.
Full textAbstract:
Le rétinoblastome est une tumeur maligne de la rétine qui touche essentiellement les nourrissons et jeunes enfants. Sa prise en charge est associée à la survenue d’effets secondaires sévères, certains traitements induisant le développement de tumeurs secondaires. Dans ce contexte, la thérapie photodynamique (PDT) apparaît comme une alternative prometteuse, car elle est non mutagène et génère des effets secondaires moins importants. Elle consiste à injecter un agent photosensibilisateur (PS) - une porphyrine par exemple – puis à illuminer la zone tumorale avec un laser. L'efficacité de la PDT nécessite l'accumulation de PS dans la tumeur. Cependant, la plupart des porphyrines sont hydrophobes et s'agrègent en milieu aqueux. Leur incorporation dans un nano-vecteur peut améliorer leur distribution au cytoplasme. Malheureusement, lorsqu'elles sont encapsulées dans le cœur des nanoparticules, les molécules de PS perdent leur phototoxicité en raison de leur auto-extinction. Dans ce travail, nous avons conçu des lipo-nanoparticules biodégradables (LNP) constituées d'une nanoparticule (NP) de poly (D,L)-lactide (PLA) recouverte d'une bicouche de phospholipides (POPC-DOTAP). Un principe actif anticancéreux, la bêta-lapachone et un agent photosensibilisateur ont ensuite été co-encapsulés dans notre système en vue de favoriser un effet synergique sur le rétinoblastome. Nous avons démontré la formation effective des LNPs et leur internalisation dans les cellules de rétinoblastome en quelques heures.Enfin, nous avons démontré une amélioration de l'activité antitumorale en combinant les deux traitement dans notre système par rapport au traitement simple par PDT ou chimiothérapieRetinoblastoma is a malignant tumor of the retina in infants. Conventional therapies are associated to severe side effects and some of them induce secondary tumors. Therefore, photodynamic therapy (PDT) appears as a promising alternative as it is non-mutagenic and generates minimal side effects. It consists in injection of a photosensitizer (PS) like a porphyrin, and then illumination of the tumor area with a laser. The effectiveness of PDT requires the accumulation of the PS in the tumor. However, most porphyrins are hydrophobic and aggregate in aqueous medium. Their incorporation into a nanocarrier may improve their delivery to the cytoplasm. Unfortunately, when incorporated into a nanoparticle core, PS molecules lose their phototoxicity due to self-quenching. In this work, we have designed biodegradable liponanoparticles (LNPs) consisting of a poly(D,L)-lactide (PLA) nanoparticle (NP) coated with a phospholipid (POPC/DOTAP) bilayer. An anticancer drug, beta-lapachone (β-Lap), and a photosensitizer were then co-encapsulated in these LNPs for achieving synergistic effect on retinoblastoma. We have first demonstrated the effective formation of the LNPs and their internalization in retinoblastoma cells within few hours. Then we studied the cyto/phototoxicity of the system.The hybrid nanoparticles showed an improved antitumor activity when the PS and β-Lap were combined, compared to the single treatment by PDT or chemotherapy
34
Reichel, Derek Alexander. "HALO- AND SOLVATO-FLUOROCHROMIC POLYMER NANOASSEMBLIES FOR CANCER THERANOSTICS." UKnowledge, 2017. http://uknowledge.uky.edu/pharmacy_etds/74.
Full textAbstract:
Theranostics is an emerging treatment approach that combines diagnostics with therapy in order to personalize treatment regimens for individual patients and decrease cancer mortality. Previously, nanoparticles entrapping conventional fluorescent dyes were developed for cancer theranostics, but fluorescent nanoparticles did not allow clinicians to significantly improve cancer treatments.
The use of fluorescent dyes that are sensitive to solvent acidity (halo-fluorochromism) and polarity (solvato-fluorochromism) may overcome the limitations of fluorescent nanoparticles and improve cancer therapy by enabling researchers to detect chemical properties within the nanoparticle core environment. The model halo- and solvato-fluorochromic dye Nile blue was attached to the core of nanoscale drug delivery systems called polymer nanoassemblies (PNAs), which were created by tethering hydrophilic polymers and hydrophobic groups to a cationic polymer scaffold. The fluorescence of empty PNAs increased by 100% at pH 5.0 compared to pH 7.4, and the fluorescence of drug-loaded PNAs increased up to 300% compared to empty PNAs. A comparison of the fluorochromic properties between PNAs with various core properties indicated that both hydrophobic pendant groups and scaffold amines contributed to the fluorochromism of PNAs.
The halo-fluorochromism of PNAs allowed investigators to minimize the detection of fluorescence signals in healthy organs such as the liver. Fluorescence imaging of halo-fluorochromic PNAs diffused into tissue mimics indicated that fluorescence of PNAs in tissues increased by 100% at pH 7.0 compared to pH 7.4. In addition, halo-fluorochromic PNAs identified the acidic perimeter surrounding metastatic tumors in orthotopic metastatic tumor models. Computational simulations of metastatic lesions verified that some halo-fluorochromic PNAs accumulate in the hypoxic/acidic regions of metastatic tumors following intravenous administration. These simulations also indicated that the accumulation of PNAs in the hypoxic regions of tumors doubles at 12 hours post-treatment compared to 1.8 hours post-treatment.
The solvato-fluorochromism of PNAs enabled the fluorescence-based measurement of drug release from the nanoassembly core during dialysis-based drug release measurements. Solvato-fluorochromic methods indicated faster drug release rates than HPLC-based methods. Mechanistic modeling of drug release indicated that solvato-fluorochromic methods were unaffected by released drugs that interfered with HPLC-based methods. However, mechanistic modeling also indicated that drug rebinding and diffusion did not account for all of the differences between drug release rates determined by solvato-fluorochromic- and HPLC-based methods. Based on this evidence, it was hypothesized that solvato-fluorochromic drug release methods measure drug diffusion from near the scaffold of PNAs in a small region of the nanoassembly core, and that this process contributes to overall drug release but does not indicate apparent drug release rates for PNAs.
In order to develop PNAs for potential clinical applications, ionizable amines were removed from the polymer scaffold to increase drug loading and sustain the release of model drugs carfilzomib and docetaxel. The removal of primary amines decreased drug diffusivity in the core of PNAs (D from 3.9*10-18 cm2/s to 0.1*10-19 cm2/s) and increased the drug release half-life (t1/2 from 4 to 26 hours). The controlled release of carfilzomib from PNAs reduced drug metabolism by 60% for up to one hour and sustained proteasome inhibition in cancer cells at 72 h post-treatment compared to free drug.
Overall, this work provides insight into the design of theranostic nanoparticles with beneficial properties for improving cancer treatment.
35
Lee, Kate Y. J. "Colloidal gold nanoparticles for cancer therapy: effects of particle size on treatment efficacy, toxicology, and biodistribution." Diss., Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/43640.
Full textAbstract:
Gold nanoparticle has emerged as an attractive platform for drug delivery applications by complementing the existing drug delivery carriers. Currently, only a few gold nanoparticle-based anticancer drug delivery systems have been reported, compared to the polymer-based delivery systems. Additionally, there is still a lack of understanding for the behavior and fate of the gold-drug conjugate in the body that further attention is required. The overall goal of this thesis is to investigate the in vivo behavior of colloidal gold nanoparticle and its therapeutic efficacy in an animal model, especially in a drug delivery application. To achieve this goal, we investigated the feasibility of using colloidal gold nanoparticle as an anticancer agent delivery vehicle for treatment of cancer. Then, long-term clearance, toxicity, and biodistribution of colloidal gold nanoparticle were studied to further aid in understanding of using colloidal gold nanoparticle as a drug delivery platform. In particular, two representative sizes of gold nanoparticles, 5nm and 60nm, were investigated for the size effect on the therapeutic efficacy, toxicity, biodistribution, and clearance in cancer nanotherapy.
We believe that nanoparticle size plays a critical role in not only delivering the drug to the target site but also determining the in vivo behavior such as biodistribution and clearance. By choosing an appropriate size scale for the system, we successfully used the small-sized gold nanoparticles for drug delivery applications, which also displayed no apparent toxicity with desirable clearance from the biological system. This work is significant by providing an insight on a potential ideal candidate for drug delivery carrier for cancer nanotherapy.
36
Stimphil, Emmanuel. "Technobiology Paradigm in Nanomedicine: Treating Cancer with MagnetoElectric Nanoparticles." FIU Digital Commons, 2017. https://digitalcommons.fiu.edu/etd/3546.
Full textAbstract:
Today, cancer is the world’s deadliest disease. Despite significant progress to find a cure, especially over the last decade, with immunotherapy rapidly becoming the state of the art, major open questions remain. Each successful therapy is not only limited to a few cancers but also has relatively low specificity to target cancer cells; although cancer cells can indeed be eradicated, many normal cells are sacrificed as collateral damage. To fill this gap, we have developed a class of multiferroic nanostructures known as magnetoelectric nanoparticles (MENs) that can be used to enable externally controlled high-specificity targeted delivery and release of therapeutic drugs on demand. First, the underlying physics of MENs was studied, as it relates to different externally applied sequences of a.c and d.c. magnetic fields to facilitate (i) high-specificity targeting driven by a physical force rather than antibody matching, (ii) a delivery mechanism that enhances cellular uptake (via nanoelectroporation) of therapeutic drugs across the cellular membrane of cancer cells only, and (iii) an externally controlled mechanism that releases the therapeutic drug on-demand. Secondly, the application of MENs as a nuclear magnetic resonance (NMR) nanoprobe was explored. The intrinsically coupled ferromagnetic and ferroelectric phases allowes the nanoparticle to be used as sensitive nanoprobe detectors of biological cells; based on the knowledge that the cellular membrane is an electrically charged medium which creates an ideal environment for MENs to distinguish between cancer and normal cells. Lastly, through in-vivo and in-vitro studies, MENs were used as drug delivery vehicle capable of crossing the blood brain barrier (BBB) and delivering recently discovered MIA690 peptide drug (via nanoelectroporation) to glioblastoma multiforme (GBM) brain cancer cells. Glioblastomas are tumors that arise from astrocytes in the brain; that are highly malignant and reproduces quickly due to their large network of blood vessels. In the following study, we report the binding efficacy of MIA690 to magnetoelecric nanoparticles as well as present an unprecedented targeted and on-demand release to glioblastoma cells through special sequences of a.c. and d.c. magnetic fields. The potential therapeutic and diagnostic impact of MENs for future medicine is beyond the scope of this study, as MENs can be used to treat any type of cancer.
37
Swisher, Luxi Zhang. "Development of nanoscale biosensors for cancer related proteases and blood-borne pathogens based on electrochemical and optical methods." Diss., Kansas State University, 2015. http://hdl.handle.net/2097/19057.
Full textAbstract:
Doctor of PhilosophyDepartment of Chemistry
Jun Li
A lot of materials exhibit novel properties when scaled down to nanoscale. Here we explore nanoelectrode arrays (NEAs) and nanoparticles in the application of high performance biosensors. We have developed an electrochemical (EC) method for measuring the activity of proteases using vertically aligned carbon nanofiber (VACNF) NEAs. VACNFs were grown on conductive substrates and encapsulated in SiO₂ matrix. After polishing and plasma etching, controlled VACNF tips are exposed to form an embedded NEA. Tetrapeptides specific to cancer-mediated proteases are covalently attached to the exposed tip, with a ferrocene (Fc) moiety linked at the distal end. The redox signal of Fc can be measured with AC voltammetry (ACV) at ~1 kHz frequency, showing distinct properties from macro-electrodes due to VACNF's unique interior structure. The enhanced ACV properties enable the kinetic measurements of proteolytic cleavage of the surface-attached tetrapeptides by proteases. The well-defined regular VACNF NEAs by e-beam lithography show a much faster kinetics for cathepsin B proteolysis. This EC method was further applied in whole lysate of human breast tissue and breast cells. The detected protease activity was found increased in cancer cells, with the metastatic cancer cell lysate showing the highest cathepsin B activity. The results indicated the potential of this technique as a portable multiplex electronic device for cancer diagnosis and treatment monitoring through rapid profiling of the activity of specific cancer-relevant proteases. In another exploratory study, we modified nanoparticles with luminol and viral nucleic acid to develop chemiluminescence (CL) biosensors for blood-borne pathogens. Luminol-labeled 10-nm-diameter gold nanoparticles (GNPs) served as a nanocarrier for enhancing CL signal. The CL signal can be observed over 8 orders of magnitude variations in GNP concentration. Using the same number of particles, luminol-labeled 30-nm-diameter latex beads showed ~3 orders of magnitude higher CL compared to 10-nm-diameter GNPs. Hybridization of target H1N1 nucleic acid on the latex beads and probe nucleic acid on the glass or optical fiber surface has been achieved. This assay will be incorporated into a simple hand-held device for routine assays in hospitals and clinics, or for large-scale screening of human populations as diagnostic tools to identify specific viral strains.
38
Lee, Karin L. "High Aspect Ratio Viral Nanoparticles for Cancer Therapy." Case Western Reserve University School of Graduate Studies / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=case1467714833.
Full text
39
Hauser, Anastasia K. "PEPTIDE-FUNCTIONALIZED MAGNETIC NANOPARTICLES FOR CANCER THERAPY APPLICATIONS." UKnowledge, 2016. http://uknowledge.uky.edu/cme_etds/59.
Full textAbstract:
Lung cancer is one of the leading causes of cancer deaths in the United States. Radiation and chemotherapy are conventional treatments, but they result in serious side effects and the probability of tumor recurrence remains high. Therefore, there is an increasing need to enhance the efficacy of conventional treatments. Magnetic nanoparticles have been previously studied for a variety of applications such as magnetic resonance imaging contrast agents, anemia treatment, magnetic cell sorting and magnetically mediated hyperthermia (MMH). In this work, dextran coated iron oxide nanoparticles were developed and functionalized with peptides to target the nanoparticles to either the extracellular matrix (ECM) of tumor tissue or to localize the nanoparticles in subcellular regions after cell uptake.
The magnetic nanoparticles were utilized for a variety of applications. First, heating properties of the nanoparticles were utilized to administer hyperthermia treatments combined with chemotherapy. The nanoparticles were functionalized with peptides to target fibrinogen in the ECM and extensively characterized for their physicochemical properties, and MMH combined with chemotherapy was able to enhance the toxicity of chemotherapy.
The second application of the nanoparticles was magnetically mediated energy delivery. This treatment does not result in a bulk temperature rise upon actuation of the nanoparticles by an alternating magnetic field (AMF) but rather results in intracellular damage via friction from Brownian rotation or nanoscale heating effects from Neél relaxations. The nanoparticles were functionalized with a cell penetrating peptide to facilitate cell uptake and lysosomal escape. The intracellular effects of the internalized nanoparticles alone and with activation by an AMF were evaluated.
Iron concentrations in vivo are highly regulated as excess iron can catalyze the formation of the hydroxyl radical through Fenton chemistry. Although often a concern of using iron oxide nanoparticles for therapeutic applications, these inherent toxicities were harnessed and utilized to enhance radiation therapy. Therefore, the third application of magnetic nanoparticles was their ability to catalyze reactive oxygen species formation and increase efficacy of radiation. Overall, iron oxide nanoparticles have a variety of cancer therapy applications and are a promising class of materials for increasing efficacy and reducing the side effects of conventional cancer treatments.
40
Gilliland, Stanley E. III. "Synthesis, Surface Functionalization, and Biological Testing of Iron Oxide Nanoparticles for Development as a Cancer Therapeutic." VCU Scholars Compass, 2015. http://scholarscompass.vcu.edu/etd/4024.
Full textAbstract:
Iron oxide nanoparticles are highly researched for their use in biomedical applications such as drug delivery, diagnosis, and therapy. The inherent biodegradable and biocompatible nanoparticle properties make them highly advantageous in nanomedicine. The magnetic properties of iron oxide nanoparticles make them promising candidates for magnetic fluid hyperthermia applications. Designing an efficient iron oxide nanoparticle for hyperthermia requires synthetic, surface functionalization, stability, and biological investigations. This research focused on the following three areas: optimizing synthesis conditions for maximum radiofrequency induced magnetic hyperthermia, designing a simple and modifiable surface functionalization method for specific or broad biological stability, and in vitro and in vivo testing of surface functionalized iron oxide nanoparticles in delivering effective hyperthermia or radiotherapy.
The benzyl alcohol modified seed growth method of synthesizing iron oxide nanoparticles using iron acetylacetonate as an iron precursor was investigated to identify significant nanoparticle properties that effect radiofrequency induced magnetic hyperthermia. Investigation of this synthesis under atmospheric conditions revealed a combination of thermal decomposition and oxidation-reduction mechanisms that can produce nanoparticles with larger crystallite sizes and decreased size distributions.
Nanoparticles were easily surface functionalized with (3-Glycidyloxypropyl)trimethoxysilane (GLYMO) without the need for organic-aqueous phase transfer methods. The epoxy ring on GLYMO facilitated post-modifications via a base catalyzed epoxy ring opening to obtain nanoparticles with different terminal groups. Glycine, serine, γ-aminobutryic acid (ABA), (S)-(-)-4-amino-2-hydroxybutyric acid (SAHBA), ethylenediamine, and tetraethylenepentamine were successful in modifying GLYMO coated-iron oxide nanoparticles to provide colloidal and varying biological stability while also allowing for further conjugation of chemotherapeutics or radiotherapeutics. The colloidal stability of cationic and anionic nanoparticles in several biologically relevant media was studied to address claims of increased cellular uptake for cationic nanoparticles.
The surface functionalized iron oxide nanoparticles were investigated to determine effects on cellular uptake and viability. In vitro tests were used to confirm the ability of iron oxide nanoparticles to provide effective hyperthermia treatment. S-2-(4-Aminobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid (DOTA) was coupled to SAHBA and carboxymethylated polyvinyl alcohol surface functionalized iron oxide nanoparticles and radiolabeled with 177Lu. The capability of radiolabeled iron oxide nanoparticles for delivering radiation therapy to a U87MG murine orthotopic xenograft model of glioblastoma was initially investigated.
41
Foy, Susan Patricia. "Multifunctional Magnetic Nanoparticles for Cancer Imaging and Therapy." Case Western Reserve University School of Graduate Studies / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=case1319836040.
Full text
42
Smith, Bryan Ronain. "Nanoparticulate platforms for molecular imaging of atherosclerosis and breast cancer." Columbus, Ohio : Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1150309580.
Full text
43
Hollis, Christin P. "NANOCRYSTALS OF CHEMOTHERAPEUTIC AGENTS FOR CANCER THERANOSTICS: DEVELOPMENT AND IN VITRO AND IN VIVO EVALUATION." UKnowledge, 2012. http://uknowledge.uky.edu/pharmacy_etds/17.
Full textAbstract:
The majority of pharmacologically active chemotherapeutics are poorly water soluble. Solubilization enhancement by the utilization of organic solvents often leads to adverse side effects. Nanoparticle-based cancer therapy, which is passively targeted to the tumor tissue via the enhanced permeation and retention effect, has been vastly developed in recent years. Nanocrystals, which exist as crystalline and carry nearly 100% drug loading, has been explored for delivering antineoplastic agents. Additionally, the hybrid nanocrystal concept offers a novel and simple way to integrate imaging agents into the drug crystals, enabling the achievement of theranostics. The overall objective of this dissertation is to formulate both pure and hybrid nanocrystals, evaluate their performance in vitro and in vivo, and investigate the extent of tissue distribution and tumor accumulation in a murine model. Pure and hybrid nanocrystals of several model drugs, including paclitaxel (PTX), camptothecin, and ZSTK474, were precipitated by the antisolvent method in the absence of stabilizer, and their size was further minimized by homogenization. The nanocrystals of PTX, which is the focus of the study, had particle size of approximately 200 nm and close-to-neutral surface charge. Depending on the cell type, PTX nanocrystals exerted different level of cytotoxicity. In human colon and breast cancer xenograft models, nanocrystals yielded similar efficacy as the conventional formulation, Taxol, at a dose of 20 mg/kg, yet induced a reduced toxicity. Biodistribution study revealed that 3H-PTX nanocrystals were sequestered rapidly by the macrophages upon intravenous injection. Yet, apparent toxicity was not observed even after four weekly injections. The sequestered nanocrystals were postulated to be released slowly into the blood circulation and reached the tumor. Tritium-labeled-taxol, in contrast, was distributed extensively to all the major organs, inducing systemic toxicity as observed in significant body weight loss. The biodistribution results obtained from radioactive analysis and whole-body optical imaging was compared. To some degree, the correlation was present, but divergence in the quantitative result, due to nanocrystal integrity and limitations associated with the optical modality, existed. Despite their promising properties, nanocrystal suspensions must be securely stabilized by stealth polymers in order to minimize opsonization, extend blood-circulation time, and efficiently target the tumor.
44
Abayaweera, Gayani Sandeepa. "Diverse use of iron oxide nanoparticles for anticancer therapy." Diss., Kansas State University, 2014. http://hdl.handle.net/2097/17564.
Full textAbstract:
Doctor of PhilosophyDepartment of Chemistry
Stefan H. Bossmann
Recent development of a variety of superparamagnetic and ferromagnetic iron/iron oxide (Fe/Fe₃O₄) nanoparticles with different surface chemistry have been widely studied for numerous biological applications such as drug delivery, as diagnostics, hyperthermia and magnetic resonance imaging. The wide applications of Fe/Fe₃O₄ nanoparticles are possible since they exhibit favorable properties as high magnetization ability, are smaller than 100 nm in size, they can be coated with several ligands which allow drug delivery at a specific site and are biocompatible. By using Fe/Fe₃O₄ nanoparticles as drug delivery agents treatment costs and side effects can be reduced, however treatment efficacy can be increased. We have demonstrated that Fe/Fe₃O₄ nanoparticles can be utilized in different methods depending on their properties, to be used as therapeutic agents for cancer treatment. In one method we have taken advantage of the Fe/Fe₃O₄ nanoparticles magnetic ability to produce hyperthermia (heat) in cancer cells when subjected to an alternative magnetic field. Here we use the cell based delivery system since the size of the nanoparticles are small they can be taken up by monocyte/ macrophage like cells for systemic transportation to the inflamed cancer cite. The hyperthermia study was conducted in mice with pancreatic cancer. This study demonstrated that the life expectancy of the mice increased by 31%. In the next method we took the advantage of the surface chemistry of the Fe/Fe₃O₄ nanoparticles and changed it with dopamine-peptide and dopamine-thiosemicarbazone ligands. The advantage of the peptide is to deliver the nanoparticle to its target site and the thiosemicarbazone analogue is used as an iron chelator that would initiate apoptosis in cancer cells. This nanoplatform was tested in 4T1 breast cancer cell line and normal fibroblast cell line and demonstrated that it was effective towards the cancer cell line than the normal cell line at a ratio of 5:1 of thiosemicarbazone analogue : dopamine on the nanoparticle. However further studies are needed to be done to clarify the effectiveness of this nanosystem.
45
Xue, Ruipeng. "Nanofiber Based Optical Sensors for Oxygen Determination." The Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1405508835.
Full text
46
Engelbrecht, Monique. "The interaction between 6 MV X-rays and p(66)/Be neutrons with spherical gold nanoparticles to induce cellular damage." University of the Western Cape, 2016. http://hdl.handle.net/11394/5550.
Full textAbstract:
Magister Scientiae (Medical Bioscience) - MSc(MBS)Despite the advances in therapies such as chemotherapy and radiotherapy, tumours have been shown to be resistant to the treatments. Gold nanoparticles (AuNPs) have been recognized as effective radiosensitizers of low energy (e.g. 200–500 kV) X-rays, leading to the emission of Auger electrons that cause highly localised ionizing damage to cells. Spherical AuNPs were synthesised via the reduction of the chloroaurate ions by sodium citrate. Characterisation of AuNPs involved UV-visible spectrophotometry, zeta (Z) potential, dynamic light scattering (DLS) and polydispersity index (PDI) measurements for determination of surface plasmon resonance (SPR), surface charge and stability, as well as transmission electron microscopy (TEM) for hydrodynamic core sizes, size distribution width and shape of AuNPs. Both the 5 and 10 nm AuNPs were found to be anionic with λmax absorbance of 525 nm and uniform size distribution. DLS measurement at 38.12 nm and 48.50 nm, respectively for 5 nm and 10 nm AuNPs, points to aggregation of the AuNPs. However, TEM measurements confirmed the core size of the 10 nm AuNPs. Non-malignant Chinese hamster ovary (CHO-K1), brain endothelial (BEnd5), breast (MCF-10A), isolated human lymphocytes and malignant breast (MCF-7) cell lines were treated with 50 μg/ml of AuNPs, and irradiated with either 1, 2 or 4 Gy X-rays or 1 or 2 Gy p(66)/Be neutron radiation. The γ-H2AX foci assay, cytokinesis-block micronucleus assay, MTT assay and fluorescence-activated cell sorting (FACS) was used to determine that amount of double stranded breaks (DSBs) in isolated lymphocytes, the presence and number of micronuclei (MNi) within binucleated cells (BNCs), cell viability and cell cycle progression, respectively. Preliminary experiments that established the reliability of the study regarding the induction of DNA damage after the bombardment of AuNPs by scattered low kV X-rays, were carried out on lymphocytes. Combined treatment (AuNPs and radiation) resulted in more endogenous foci in comparison to lymphocytes that were treated with AuNPs only. The CHO-K1 and MCF-7 cells showed higher MNi frequencies after the combination treatment of AuNPs and radiation compared to the number of MNi in samples exposed to AuNPs and radiation separately. The AuNPs alone influenced the cellular kinetics of all cell types. Interaction indices, which is the enhancement factor of AuNPs in combination with radiation, for AuNPs and 6 MV 2 Gy X-rays of 1.6 to 1.7 and 1.3 to 1.4 have respectively been determined for CHO-K1 and MCF-7 cells, whilst that for the other cell types used in the study were not different from Unity. As expected, the interaction indices between AuNPs and p(66)/Be neutrons was lower than the interaction indices after 2 Gy X-rays, as p(66)/Be neutrons interact only with the nuclei of the AuNP's atoms and the X-ray photons interact with the orbital electrons of the atoms of the AuNPs leading to Auger electron emission. The cell viability assay showed that 50 μg/ml of AuNPs had an inhibitory effect on cellular proliferation, in all four cell linnes whereas the lower concentrations (2.5, 5 and 10 μg/ml) had no effect. Results in this study, revealed an increase in the accumulation of CHO-K1 an MCF-7 cells in the G₂/M phase of the cell cycle after being treated with AuNPs followed by X-ray radiation, suggesting that the cells have possibly been sensitised to the damaging effects of radiation. Further studies are required to quantify internalised AuNPs and to then link the possible concentration differences of the AuNPs to differences in radiation damage effects observed for the different cell types.
47
Kharin, Alexander. "Group IV nanoparticles for cell imaging and therapy." Thesis, Lyon, 2016. http://www.theses.fr/2016LYSE1032/document.
Full textAbstract:
La biomédecine et la biophotonique sont des champs de recherches en plein expansion qui grandissent à vive allure, constituant un secteur entier d'activités novatrices. Ce secteur, vraiment interdisciplinaire, comprend le développement de nouveaux nanomatériaux, de sources lumineuses et l'élaboration de nouveaux concepts, de dispositifs/équipements pour quantifier la conversion de photons et leurs interactions. L'importance décisive du diagnostic précoce et du traitement individuel des patients exige des thérapies soigneusement ciblées et la capacité de provoquer sélectivement la mort cellulaire des cellules malades. Malgré les progrès spectaculaires réalisés en utilisant les points quantiques ou des molécules biologiques organiques pour l'imagerie biologique et la libération ciblée de médicaments, plusieurs problèmes restent à résoudre : obtenir une sélectivité accrue pour une accumulation spécifique dans les tumeurs et une amélioration de l'efficacité des traitements. D'autres problèmes incluent la cytotoxicité et la génotoxicité, l'élimination lente et la stabilité chimique imparfaite. Des espérances nouvelles sont portées par de nouvelles classes de matériaux inorganiques comme les nanoparticules à base de silicium ou à base de carbone, qui pourraient faire preuves de caractéristiques de stabilité plus prometteuses tant pour le diagnostic médical que pour la thérapie. Pour cette raison, la découverte de nouveaux agents de marquage et de transport de médicaments représente un champ important de la recherche avec un potentiel de croissance renforcéBiomedicine and biophotonics related businesses are currently growing at a breathtaking pace, thereby comprising one of the fastest growing sectors of innovative economy. This sector is truly interdisciplinary, including, very prominently, the development of novel nanomaterials, light sources, or novel device/equipment concepts to carry out photon conversion or interaction. The great importance of disease diagnosis at a very early stage and of the individual treatment of patients requires a carefully targeted therapy and the ability to induce cell death selectively in diseased cells. Despite the tremendous progress achieved by using quantum dots or organic molecules for bio-imaging and drug delivery, some problems still remain to be solved: increased selectivity for tumor accumulation, and enhancement of treatment efficiency. Other potential problems include cyto- and genotoxicity, slow clearance and low chemical stability. Significant expectations are now related to novel classes of inorganic materials, such as silicon-based or carbon-based nanoparticles, which could exhibit more stable and promising characteristics for both medical diagnostics and therapy. For this reason, new labeling and drug delivery agents for medical application is an important field of research with strongly-growing potential.The 5 types of group IV nanoparticles had been synthesized by various methods. First one is the porous silicon, produced by the electrochemical etching of bulk silicon wafer. That well-known technique gives the material with remarkably bright photoluminescence and the complicated porous structure. The porous silicon particles are the agglomerates of the small silicon crystallites with 3nm size. Second type is 20 nm crystalline silicon particles, produced by the laser ablation of the bulk silicon in water. Those particles have lack of PL under UV excitation, but they can luminesce under 2photon excitation conditions. 3rd type of the particles is the 8 nm nanodiamonds
48
Acosta, Aldo Aparicio. "Síntese e caracterização de nanopartículas de silício para uso como veiculadores de oligopeptídeos ciclo-RGDfV para tratamento de câncer." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/59/59138/tde-19052015-150230/.
Full textAbstract:
Nanopartículas luminescentes de silício poroso (NPSi) foram projetadas e preparadas por métodos de corrosão eletroquímica seguidas de ultrasonicação, em substratos de silício tipo-p, dopados com boro e com resistividades que variam de 10-20 e 1-10 ômega cm em soluções eletrolíticas compostas por ácido fluorídrico (HF) em etanol absoluto (C^2H^5OH). As condições de processamento envolvem a variação da densidade de corrente \"J\" tempo de anodização \"t\" e o controle da concentração do HF. Técnicas de microscopia eletrônica de varredura (MEV), espectroscopia de absorção UV-Vis, espectroscopia de fluorescência, difração de raios-X e medidas de potencial zeta e tamanho de partícula foram usados para investigar as propriedades morfológicas e ópticas do material resultante. Nanopartículas com diâmetros de até 150 nm foram obtidas após filtragem através de filtros de membrana. A oxidação química em soluções de peróxido de hidrogénio e ácido sulfúrico permitiu a obtenção de Nanoparticulas com emissão de fluorescência na região verde (532 nm), vermelho (630 e 650 nm) e infravermelho próximo (862 e 980 nm) do espectro eletromagnético. A associação de NPSi com RGDfV foi estudada por espectroscopia de ressonância magnética nuclear de próton (H-RMN). Um aumento na distribuição do tamanho e a intensidade de fluorescência foi observado após a funcionalização com RGDfV. Os efeitos citotóxicos do RGDfV e NPSi foram confirmados por ensaios de viabilidade celular pelo método MTT usando células de melanoma murino B16-F10 como modelo biológico. Estudos iniciais de internalização de PcCIAI por eletroporação foram realizados para futuros estudos de transfecção de moléculas de interferência (siRNA).Luminescent porous silicon nanoparticles (NPSi) were synthesized by electrochemical etching followed by ultra-sonication of 1-10 and 10-20 ohm.cm resistive p-type silicon wafers in electrolytic solutions composed by hydrofluoric acid (HF) in absolute ethanol (C2H5OH), by changing current density (J), etching time (t) and HF concentration. Scanning electron microscopy (SEM), X-ray diffraction, dynamic ligth scattering (DLS), zetasize measurement, UV-Vis absorption spectroscopy and fluorescence spectroscopy were used to investigate the morphological and optical properties of the resulting material. Nanoparticles with diameter up to 150 nm were obtained after filtered through filtration membrane. The chemical oxidation in oxidizing solutions composed by hydrogen peroxide in sulfuric acid allowed the isolation of nanoparticles with fluorescence properties as expected, with emission in green (532 nm), red (630 and 650 nm) and near infrared (862 and 980 nm) region of the electromagnetic spectrum. The association of NPSi with RGDfV was studied by nuclear magnetic resonance spectroscopy (H-NMR). The increase on size distribution and fluorescence intensity was observed after functionalization with RGDfV. The citotoxicity effects of RGDfV and NPSi was confirmed by MTT assays using B16-F10 melanoma murine cells, as a biological model. Initial studies of internalization PcClAl by electroporation were performed for future studies of transfection of interfering molecules (siRNA).
49
Twomey, Megan. "Conjugated Polymer-Based Biomaterials Through Controlled Self-Assembly." FIU Digital Commons, 2016. http://digitalcommons.fiu.edu/etd/2452.
Full textAbstract:
Synthetic polymeric materials have gained significant use as biological materials (biomaterials) in biomedical and pharmaceutical applications. As a result, a demand for well-defined polymers with tunable properties has emerged. The synthetic versatility of polymeric biomaterials allows the opportunity to understand the structure-property relationship of materials and their cellular interactions. A novel class of polymeric biomaterials are conjugated polymers (CPs), which possess desirable physicochemical and excellent photophysical properties, including inherent fluorescence. The synthetic versatility of CPs allows easy modification of the conjugated backbone to tune emission and side chain structures to adjust biocompatibility through increased water solubility, controlled biodegradability, and incorporation of targeting units. The aim of this dissertation is to better understand conjugated polymer nanoparticle (CPN) structure and self-assembly in an aqueous environment, and how those structural features affect cellular interactions to establish a structure-function relationship.
This work presents the fabrication of several different CPNs for cancer cell targeting and labelling, and differentiation of biologically important molecules. Core−shell nanoparticles were prepared using a semi-flexible cationic CPN complexed with hyaluronic acid (HA), a polyanion. The resulting CPNs exhibited high cancer cell specificity with low adsorption to normal cells, as a result of HA’s affinity towards overexpressed receptors on cancer cell surface. A systematic investigation on the aggregation properties of CPNs that vary by side chain and backbone structures in response to different biologically important anionic polysaccharides in a complex biological medium was conducted. Mitochondria-specific CPNs were fabricated from a semi-flexible CPN modified with the mitochondrial-targeting triphenylphosphonium (TPP) group. The subcellular localization and cellular toxicity were dependent on backbone flexibility, hydrophilicity, and molecular weight. Dual-targeting CPNs grafted with folic acid (FA) side chains and complexed with hyaluronic acid (HA) were fabricated for improved uptake and bioimaging of cancer cells.
The work presented here shows how modifications to CPN backbone and side chain structures modulate their cellular interactions. The physicochemical and biophysical properties of CPNs affect biocompatibility and understanding those properties will lead to the development of novel CP-based biomaterials.
50
Rhyner, Matthew N. "Development of cancer diagnostics using nanoparticles and amphiphilic polymers." Diss., Atlanta, Ga. : Georgia Institute of Technology, 2008. http://hdl.handle.net/1853/22582.
Full textAbstract:
Thesis (Ph. D.)--Biomedical Engineering, Georgia Institute of Technology, 2008.Committee Chair: Nie, Shuming; Committee Member: Bao, Gang; Committee Member: Chung, Leland; Committee Member: Murthy, Niren; Committee Member: Prausnitz, Mark.