Academic literature on the topic 'Nano contrast agents'

Les agents d’imagerie aux rayons X sont essentiels en combinaison avec la tomodensitométrie pour améliorer le contraste de manière à permettre la visualisation complète des vaisseaux sanguins et de fournir l'information structurelle et fonctionnelle de lésions permettant la détection d'une tumeur. Ces outils fondamentaux permettent également de faire la distinction entre les cellules et les agents pathogènes sains. Les agents de contraste aux rayons X commercialisés sont limités dans leur succès dans le cas du Fenestra® VC par le temps court de circulation dans le sang et celui qui est lié à l'élimination rénale rapide du corps comme dans le cas du Xenetix® (Iobitriol). Nous avons développé des agents de contraste à base d’α-tocophérol (vitamine E), de Cholécalciférol (vitamine D3), d'huile de ricin, de Capmul® MCMC8 et d’acide oléique qui sont tous dénués de toxicité, qui contiennent de l’iode sous forme de nano-émulsion et qui sont destinés à l’imagerie préclinique en μ-CT. Ces nano-émulsions formulées ont été préparées par la technique d’émulsification spontanée de basse énergie avec une légère modification pour chaque composé iodé. Ces formulations ont montré de nouvelles caractéristiques spécifiques les rendant prometteuses dans des expérimentations in vivo avec une augmentation du rapport de la toxicité et de celui des interventions thérapeutiques visées. Nous avons étudié l'effet de la taille et de la composition chimique des systèmes nanoparticulaires sur leur biodistribution, leur pharmacocinétique et leur toxicité. Ces études ont permis de mettre en évidence l’importance de la constitution chimique des agents iodés utilisés avec par exemple la vectorisation du foie dans le cas de la vitamine E et une accumulation passive dans la rate pour les formulations à base d'huile de ricin, faisant la preuve-de-concept de l'effet EPR. D'autre part, des formulations identiques ayant deux tailles de gouttelettes différentes et contenant du cholécalciférol indiquent qu’il n’y a pas de réels impacts sur la pharmacocinétique et la biodistribution mais présentaient une augmentation importante de la toxicité. Une autre étude a consisté a étudié l’effet des charges de surface des systèmes nanoparticulaires sur leur biodistribution, c’est pourquoi la nano-émulsion a été sélectionnée pour réaliser cette étude en présence d’un polymère amphiphile tel que le poly (anhydride-alt-1-octadecene maléique) (PMAO). Les résultats in vitro et les évaluations in vivo étaient tout à fait cohérents sachant que les systèmes nanoparticulaires neutres présentent moins de toxicité comparée à celles qui sont chargés négativement qui ont été capturés de manière plus importante dans les cellules causant un stress cellulaire et delà affectent la toxicité. Selon les résultats, elles présentent des biodistributions et des pharmacocinétiques différentes. Dans ce contexte, pour la première fois, nous avons pu fonctionnaliser les nanogouttes des nanoémulsions en fixant des ligands par des liaisons covalentes. Nous avons conçu des nanogouttes enrobées avec un enrobage de silice terminé par des groupements aminés et ainsi réalisé la formation de liaisons amides avec le greffage d’un colorant modèle (colorant bleu coumarine). La quantification des groupements aminés a été réalisée à l'aide de techniques spectroscopiques et microscopiques ainsi que la détermination de l'efficacité du greffage déterminé à 41%. [...] Un de nos objectifs réalisés était de concevoir des systèmes nanoparticulaires polymères multifonctionnels qui peuvent encapsuler des principes actifs hydrophobes modèles et des agents de contraste pour l’imagerie à rayons X, de sorte à construire des dispositifs théranostiques. Pour conclure, de nouveaux agents de contraste et des systèmes de délivrance ont été synthétisés ayant des caractéristiques physico-chimiques exceptionnelles et acceptables pour être utilisées in vivo avec une grande efficacité et une faible toxicité<br>X-ray imaging agents are essential in combination with X-ray computed tomography to improve contrast enhancement aiming at providing complete visualization of blood vessels and giving structural and functional information on lesions allowing the detection of a tumor. As well as it is fundamental tool to discriminate between healthy cells and pathogens. We successfully limit the problems presented in commercial Xray contrast agents like poor contrasting in Fenestra® VC associated with short blood circulation time and to avoid rapid renal elimination from the body as found in Xenetix (Iobitriol). We developed nontoxic and blood pool iodine-containing nano-emulsion contrast agents serving in preclinical X-ray μ-CT imaging such as, α- Tocopherol (vitamin E), Cholecalciferol (vitamin D3), Castor oil, Capmul MCMC8 oil and oleic acid. Those formulated nanoemulsions were prepared by low energy spontaneous emulsification technic with slight modification for each platform. They showed new specific features rendering them promising agents in in vivo experiments as improving the balance between the efficacy and the toxicity of targeted therapeutic interventions. We investigate the effect of size and the chemical composition of the nanoparticles on their biodistribution, pharmacokinetics and toxicity. They demonstrated that the chemical structures of the droplet’s cores have significant role in targeting for example vitamin E was mainly accumulated in liver and castor oil formulation was passively accumulated in spleen explaining the proof-of-concept of EPR effect. On the other hand, two different platform sizes of Cholecalciferol molecule revealing that no real impact on the pharmacokinetics and biodistribution but presented remarkable effect on the toxicity. Of particular interest is studying the effect of the surface charge of nanoparticles on their biodistribution, this is why oleic acid nano-emulsion was selected to proceed this study by presence of amphiphilepolymer poly(maleic anhydride-alt-1-octadecene) (PMAO). The in vitro results and in vivo evaluations were completely coherent approving that the neutral charged NPs are less toxic compared to the negatively charged ones that were highly uptaked in the cells causing stress to the cells and thereby affecting the toxicity. As a result they are different in biodistribution and pharmacokinetics. In this context, for the first time, we were able to functionalize the nano-emulsion droplets with ligand molecules by covalent bonds. Likewise we designed nano-droplets and coated by silica shell ended by amino groups and then followed by formation of amide bonds with grafting to dye ligand model (coumarin blue dye). The quantification of amino groups was performed by using spectroscopic and microscopic techniques, with a grafting efficiency as high as 41%. This process improves the targeting properties of such chemotherapeutic agents to the location of interest following active targeting mechanism (ligand receptorstrategy). One of our achieved objectives was to engineer multifunctional polymer-based NPs encapsulating hydrophobic drug model as DDs and iron oxide NPs as a theranostic model. To conclude, novel contrast agents and delivering systems were synthesized with outstanding physicochemical characteristics and suitable for in vivo medium with high efficacy and low toxicity

Magnetic resonance imaging (MRI) has become a powerful clinical modality in diagnostic medicine. It is non-invasive and offers high spatial and temporal resolution. The goal of molecular imaging is to reveal the pathophysiology underlying the observed anatomy and diagnose diseases. The detection of pathological biomarkers can lead to early recognition of diseases and improved monitoring for recurrence. Clinically available contrast agents are limited in their discrimination of contrast between tissues and they tend to have very high detection limits. Because biomarkers are very low in concentration there is a need for high payload deposition of contrast agent (CA) and targeted imaging. Encapsulating discrete Gd3+ chelates in nano assembled capsules (NACs) is a simple and effective method of preparing an MRI contrast agent capable of delivering a large payload of high relaxivity imaging agent. The preparation of contrast agent containing NACs had previously focused on preparations incorporating GdDOTP5- into the internal aggregate. In this report we demonstrate that other Gd3+ chelates bearing overall charges as low as 2- can also be used to prepare NACs. This discovery opens up the possibility of using Gd3+ chelates that have inner-sphere water molecules that could further increase the relaxivity enhancement associated with the long rotational correlation time (TR) that arises from encapsulation. However, encapsulation of the q = 1 chelate GdDTPA2- afforded the same increase in relaxivity as the outer-sphere chelate GdTTHA3-. This leads us to the conclusion that in the NAC interior proton transport is not mediated by movement of whole water molecules and the enhanced relaxivity of Gd3+ chelate encapsulated within NACs arises primarily from second sphere effects. The nano assembled capsule platform has been further expanded by an alternative coating method, a new cross linked peptidic shell reported in this work affords robust capsules and exceptionally high per Gd3+ relaxivities (70.7 mM-1s-1). The availability of free amines on the surface of these capsules can be exploited to attach targeting moieties. This was demonstrated through the reaction of fluorescein isothiocyanate (FITC), an intense green emitting dye, with these amines. Green emission from the capsules indicated that surface amines were accessible to FITC. Unlike T1-shortening contrast agents, paraCEST agents can be switched on and off by the imaging scientist by turning on and off a pre-saturation pulse. This affords the ability to acquire both pre- and post-contrast images even after administration of a paraCEST contrast agent. This could potentially eliminate problems co-registering pre- and post-contrast images. A reverse NAC may allow a cationic paraCEST contrast agent to be incorporated in a high payload NAC. We were successful in synthesizing a reverse capsule using DyDOTAM3+, a paraCEST agent, and the negatively charged polymer polyacrylate and encapsulated with SiO2 nanoparticles. These initial preparations of reverse NACs were not able to generate CEST contrast however.

Les maladies cardio-vasculaires liées à l'athérosclérose sont pourvoyeuses d’une importante morbi-mortalité dans les pays développés. Une détection plus précoce des modifications des parois vasculaires, via des techniques de diagnostic non invasives, pourrait sensiblement améliorer leur prise en charge. L'échographie est largement utilisée comme outil de dépistage des maladies cardiovasculaires. Cependant, sa faible sensibilité limite son utilisation. Le développement d’agent de contraste spécifique permettant de résoudre ce problème semble donc primordial. Le fucoidane est un ligand polysaccharidique sulfaté ayant une forte affinité pour la P-sélectine. Exprimée au niveau de la surface des plaquettes activées et des cellules endothéliales, cette dernière est impliquée dans la pathogénèse précoce des maladies cardiovasculaires. Le but de ce projet de thèse a été de développer un agent de contraste injectable ciblant la P-sélectine via le fucoidane dans le but de réaliser une modalité d’imagerie moléculaire de faible coût, simple et spécifique des pathologies artérielles. Trois types d'agents de contraste ont été développés : 1) Des nanoparticules associées à du bromure de perfluorooctyle (PFOB), fonctionnalisées par du fucoidane. Elles ont été capables de se fixer à la P-selectine et une amélioration du contraste a été observée présentaient une mauvaise échogénicité dans la circulation sanguine, probablement en raison de leur faible teneur en PFOB et de leur très petite taille. 2) Afin d’améliorer l’échogénicité, des microcapsules contentant du PFOB dans leur coeur ont été développées. Celles-ci se sont également liées à la P-sélectine même en condition de dans un modèle animal de maladie artérielle. Cependant, ces produits flux sanguin. Des résultats dans les zones où la P-sélectine était exprimée. Malheureusement, l'augmentation du ont montré que ces m icrocapsules étaient présentes contraste était toujours insuffisante pour être suffisamment discriminante. 3) Des microbulles fonctionnalisées par du fucoidane, ont été conçues pour surmonter ce problème d’échogénicité. Elles ont montré une augmentation significative du signal acoustique en condition de flux sanguin. De plus, ces microbulles se sont accumulées à la surface des parois artérielles riches en thrombus. Ces derniers résultats indiquent que ces microbulles, en tant qu'outil d'imagerie moléculaire ultrasonore, pourraient être très intéressantes pour les futures études des maladies artérielles<br>Cardiovascular diseases due to atherosclerosis remain a major morbidity in developed countries. Their treatment could be substantially improved with early detection of the vascular Ultrasonography is widely used as a screening tool in clinic to detect cardiovascular diseases. However, its low resolution requires the development of targeted acoustic tracers to improve the contrast degree. Fucoidan is a sulfated polysaccharide ligand with a high affinity for P-selectin, which was found to be expressed on the activated non- pathological changes by invasive diagnostic techniques. platelets and endothelial cells and involved in the early pathogenesis of cardiovascular diseases. The aim of this doctoral project was to develop injectable, low-cost and simple contrast agents, functionalized with fucoidan as efficient acoustic tracers of P-selectin for ultrasound molecular imaging of arterial pathologies. Three types of contrast agents have been developed: 1) Fucoidan functionalized nanoparticles loaded with perfluorooctyl bromide (PFOB). They could bind to P-selectin and exhibit contrast enhancement in animal models of arterial disease. However, these products showed poor echogenicity in blood stream due probably to low content of PFOB and their very small size. 2) Fucoidan functionalized microcapsules with PFOB core were developed to improve the PFOB encapsulation efficiency. They could bind to P-selectin in arterial flow conditions, and microcapsules were located in the regional expression of P-selectin. Unfortunately, results revealed that these the contrast enhancement was still insufficient to be observed. 3) To address echogenicity problems, fucoidan functionalized polymer microbubbles were designed to replace PFOB. They showed strong signal enhancement under flow conditions and could accumulate on the surface of platelets-rich thrombus. These results indicated that these microbubbles, as ultrasound molecular imaging tools, could be very interesting for the future study of arterial diseases

L’objectif de cette thèse est de réaliser un agent de contraste vasculaire pour tomodensitométrie utilisable en préclinique. En collaboration avec le laboratoire de biogalénique de Strasbourg, ce travail a permis d’obtenir des nano-émulsions iodées produites par diffusion spontanée de surfactif et des nanoparticules iodées produites par ”émulsion - diffusion de solvant”, comme agent de contraste vasculaire. Ces émulsions et particules polymériques présentent en effet, un temps de rémanence vasculaire de plusieurs heures, un pouvoir contrastant suffisant pour un usage en tomodensitométrie (compris entre 170 et 400 HU), la possibilité de les administrer par intraveineuse et une stabilité de plusieurs mois. Les nano-émulsions, notamment celles produites à partir de Lipiodol®, sont les plus prometteuses comme agents de contraste vasculaire de par leur forte radiopacité (475 ± 30 HU) et leur rémanence vasculaire (T1/2 of 4.1 ± 1.10 h). Les nanoparticules iodées à base de PCL présentent un pouvoir contrastant inférieur (168 ± 13 HU) mais elles sont connus pour leur capacité à modifier la libération du principe actif encapsulé. De ce fait même si les agents de contraste de nature lipidique ou ceux inorganiques sont plus performant, elles restent intéressantes pour une visualisation rapide de la distribution du principe actif dans l’organisme. Cette thèse par ailleurs, apporte plusieurs éléments pour la compréhension de la formulation des nano-émulsions obtenues par diffusion spontanée de surfactif et celle des nanoparticules produites par ”émulsion - diffusion de solvant”. Concernant les nano-émulsions, l’influence de l’iodation des huiles et du surfactif a été étudiée autant sur le plan pharmacotechnique que ceux toxicologique et pharmacocinétique. Concernant les nanoparticules à base de PCL, nous avons montré que l’impact du type d’huile et de l’iodation, des polymères PCL et PCL-mPEG et de diverses méthodes de concentration sur la formulation<br>The aim of this thesis is to formulate a blood pool contrast agent for preclinical X-ray imaging application. In collaboration with the galenic laboratory of Strasbourg, this work has allowed to obtain iodinated nano-emulsions produced by spontaneous diffusion of surfactant and nano-particles produced by iodine ”emulsion - solvent diffusion” as blood pool contrast agent. These emulsions and polymer particles present indeed a vascular persistence of several hours, a sufficient contrast to be use in computed tomography (between 170 and 400 HU), the ability to be administered intravenous and stability of several months. Nano-emulsions, including those produced from Lipiodol®, are the most promising as blood pool contrast media by their high radiopacity (475 ± 30 HU) and vascular persistence (T1/2 of 4.1 ± 1.10 h). Iodinated nano-particles of PCL have a lower X-ray attenuation (168 ± 13 HU), but they are known for their control release of the encapsulated substances. Therefore even if inorganic or lipidic contrast agents show a better contrast, they remain attractive for rapid visualization of the co-encapsulated substance distribution in the body. This thesis also introduced several features for understanding the formulation of nano-emulsions obtained by spontaneous diffusion of surfactant and the nano-particles produced by ”emulsion - solvent diffusion.”

La micro-tomodensitométrie à rayons X (dite micro-CT, CT = Computed Tomography), est une technique d’imagerie de haute résolution qui consiste d’une part à mesurer l’absorption des rayons X par les tissus, et d’autre part de reconstruire les images et les structures anatomiques en 3 dimensions par traitement informatique. L’agent de contraste est une substance capable d’améliorer la visibilité des structures d’un organe ou d’un liquide organique in vivo. Ce travail de thèse a eu pour objectif le développement d’agents de contraste iodés sous formes de nano-émulsions pour des applications précliniques en imagerie biomédicale. Nous nous sommes proposés d’étudier d’une part des nano-émulsions iodées afin d’avoir une longue rémanence vasculaire in vivo, une meilleure biocompatibilité et d’autre part de mettre au point une synthèse et une formulation plus simples que celles des agents de contraste nanoparticulaires commercialisés. Trois différentes huiles iodées ont été synthétisées et utilisées comme partie contrastante dans les nano-émulsions. Enfin, les nano-émulsions de l’α-tocophérol iodé nous ont permis d’atteindre l’objectif de cette thèse. Ces nano-émulsions iodées ont montré une très bonne biocompatibilité et combinent à la fois les propriétés d’un agent de contraste à longue rémanence vasculaire et un agent de contraste spécifique du foie<br>The X-ray microtomography (called mico-CT, CT = Computed Tomography) is a high-resolution X-ray tomography, uses X-rays to create cross-sections of a 3D-object that later can be used to recreate a virtual model without destroying the original model. The contrast agent is a substance used to enhance the contrast of structures or fluids within the body in medical imaging. The purposes of the thesis were the development of iodine-containing nano-emulsion based contrast for preclinical applications in biomedical imaging. We proposed to study blood pool contrast agents based on iodine-containing nano-emulsions and to develop simpler procedure for the preparation of these iodine-containing nano-emulsions. Three different iodinated oils were synthesized and used as the contrasting part in the nano-emulsions. Finally, nano-emulsions of iodinated α-tocopherol have been enabled us to achieve the purpose of the thesis. These iodinated nano-emulsions demonstrated very good biocompatibility and showed prolonged and significant contrast enhancement in both bloodstream and liver tissues

Dissertação (mestrado)—Universidade de Brasília, Instituto de Ciências Biológicas, Programa de Pós-Graduação em Biologia Animal, 2015.<br>Submitted by Fernanda Percia França (fernandafranca@bce.unb.br) on 2016-05-20T16:15:58Z No. of bitstreams: 1 2015_JulioCesarEloiBitencourt.pdf: 1806458 bytes, checksum: 0a8d7f915ee4b218ac6e545c68b94610 (MD5)<br>Approved for entry into archive by Raquel Viana(raquelviana@bce.unb.br) on 2016-05-20T16:54:47Z (GMT) No. of bitstreams: 1 2015_JulioCesarEloiBitencourt.pdf: 1806458 bytes, checksum: 0a8d7f915ee4b218ac6e545c68b94610 (MD5)<br>Made available in DSpace on 2016-05-20T16:54:47Z (GMT). No. of bitstreams: 1 2015_JulioCesarEloiBitencourt.pdf: 1806458 bytes, checksum: 0a8d7f915ee4b218ac6e545c68b94610 (MD5)<br>Os agentes de contraste iodados atuais causam diversos efeitos adversos e não proporcionam imageamento por período maior que trinta minutos surgindo a necessidade pela busca por agentes de contraste que diminuam os efeitos adversos e propiciem um imageamento de longo prazo. Nesse sentido o desenvolvimento de um agente de contraste iodado nanoestruturado torna-se promissor uma vez que sua estrutura nano traz por si a diminuição dos efeitos adversos e esta permite controlar o tempo que o agente de contraste permanecerá no organismo fornecendo assim um imageamento mais prolongado. O presente estudo desenvolveu uma nova formulação nanoestruturada contendo agentes de contraste iodados para a utilização em raio-x utilizando duas vias de síntese, uma com carreadores nanoestruturado lipídicos, o que posteriormente demonstrou ser inviável, e a utilização das Bases de Schiff, que demonstrou ser promissora. Os carreadores nanoestruturados lipídicos demonstraram a impossibilidade de ligação covalente do iodo ao ácido graxo, fazendo com que o iodo se deslocasse facilmente para o meio, o que é inviável para um agente de contraste. As Bases de Schiff formadas se ligaram covalentemente ao iodo fazendo com que este não fosse para o meio fornecendo a formação de um agente de contraste seguro. Antes da iodação as base de Schiff foram acopladas a moléculas de ácido graxo de sete carbonos para conferir hidrofobicidade, o que é perfeito para formação de nanoemulsão. Logo após a Base de Schiff foi iodada. As estruturas, tanto lipídicas como a Base de Schiff com acoplamento com cadeia de sete carbonos e a estrutura iodada, tiveram suas capacidades de absorção de raio-x medidas no aparelho IVIS® LUMINA XR Series III. A base de Schiff iodada demonstrou uma capacidade de absorção de raio-x de cerca de 2,17 vezes maior que a água demonstrando ser excelente para a finalidade proposta. A base de Schiff iodada com cadeias C7 nanoemulsionada obteve a absorção de raio-x de cerca de 1,22 vezes maior que a água. O acoplamento com cadeias C7 à base de Schiff trouxe a inversão da densidade do óleo fazendo com que esta se tornasse mais pesado que a água provavelmente devido ao alto peso molecular conferido a base de Schiff com o acoplamento. A partir dos resultados obtidos foi observado que a base de Schiff iodada acoplada com cadeias C7 e nanoemulsionada é promissora como agente de contraste necessitando tão somente testes in vivo para completa certificação de um novo tipo de agente de contraste nanoemulsionado no mercado.<br>Due to the current iodinated contrast agents cause many adverse effects and not offering imaging for a period longer than thirty minutes, there is a need for the search for contrast agents that reduce the adverse effects and conducive to long-term imaging. Therefore the development of a nanostructured iodinated contrast agent becomes promising since their nano structure in itself brings the reduction of adverse effects, and this allows to control the time that the contrast agent remains in the body thereby providing a longer imaging. The objective of this study was to develop a new formulation containing nanostructured iodinated contrast agents for use in computed tomography using two synthetic routes, one with nanostructured lipid carriers, which subsequently proved to be impracticable, and another synthetic route was the use of Schiff Bases which proved to be promising. The Schiff bases had their characteristics evaluated for their preparation, iodination thereof, coupling of carbon chains to give to these lipid solubility and obtaining of X-ray image by IVIS® LUMINA XR Series III machine. The Schiff base iodinated showed an x-ray absorbing capability to approximately 2,17 times greater than the water proving to be excellent for the proposed purpose. The coupling of the C7 chains brought to the Schiff base a density inversion of the oil causing it to become heavier than water probably due to the high molecular weight given to Schiff base with the coupling. This coupled Schiff sample was taken to IVIS® LUMINA XR Series III (28 Kv 100 uA) and had demonstrated its large absorption by x-ray which shows be great for a contrast agent. The Schiff base with iodine and coupling C7 was nanoemulsioned and tested in by IVIS® LUMINA XR Series III (28 Kv 100 uA) and demonstrated x-ray absorption but not as intensely as the Schiff base iodine C7 not nanoemulsioned, probably due to the dilution that the nanoemulsion suffered. From the results obtained it was observed that the Schiff base iodinated coupled with C7 and nanoemulsioned is promising as a contrast agent requiring solely in vivo tests for full certification of a new type of contrast agent in the market nanoemulsioned.

In this dissertation, research efforts mainly focused on exploring the applications of superparamagnetic iron oxide nanoparticles (SPIONs) in MR imaging and nanocatalysis via surface functionalization. A dopamine-based surface-functionalization strategy was established. The Simanek dendrons (G1 to G3), oligonucleotides and amino acids were loaded onto SPION surfaces via this approach to develop pH-sensitive MRI contrast agents, specific-DNA MR probes and a biomimetic hydrolysis catalyst. Dendron-SPION conjugates (G1 to G3) have good aqueous solubilities and high transverse relaxivities (>300 s-1*mM-1). They also showed interesting strong pH-sensitive R2 and R2* relaxivities, which were governed by the clustering states of dendron-SPIONs in different pH environments. Values of R2m and R2* m/R2m varied by over an order of magnitude around pH 5. The efficient cell-uptake (~3 million/cell) and low cytotoxicity of G1 to G3-SPIONs were demonstrated on HeLa cell cultures. The strong R2* effects were observed indicating the SPION clustering in HeLa cells. Two SPION-oligonuleotide conjugates were synthesized by coupling two half-match oligonucleotides onto domapine-capped SPIONs via SPDP linkers. They served as MR probes to detect a single-strand DNA with the same sequence to miRNA-21 based on the change of R2 values due to the DNA-bridged SPION clustering. The detection limit of the DNA could reach to 16.5 nM. A biomimetic hydrolysis nanocatalyst (i.e., Fe2O3-Asp-His complex) was developed by loading Asp and His-dopamine derivatives onto SPIONs. Paraoxon and nitrophenyl acetate were hydrolyzed under a mild condition (neutral pH, 37 °C) catalyzed by the Fe2O3-Asp-His complex. The two amino acids Asp and His cooperated with each other on the SPION surfaces to catalyze hydrolysis reactions. This catalyst could be recycled by a magnet and reused for four times without a significant loss of catalytic activity.

Advanced optical imaging techniques are emerging as useful ways to screen tissues for the presence of cancer. Plasmon resonant nanoparticles have unique optical properties that make them ideal for use as optical contrast agents. The capacity of these particles to serve a multifunctional role dependent on their composition and the intensity of incident light enables them to serve as diagnostic tools and to provide the therapeutic capability of photo-thermal energy conversion or the controlled release of an encapsulated agent. Likewise, the ability to degrade into components of a clearable size may enable the clinical translation of these types of particles.These properties were demonstrated by means of experiments in the support of three specific aims. The first specific aim was to determine whether the unique and tunable optical properties of nanorods lend them to generate signal in advanced optical imaging techniques, and that nanorods can facilitate photo-thermal conversion. The second specific aim was to show that liposomes can serve as a scaffold for the support of an array of gold nanodots to generate a structure that exhibit tunable plasmon resonant characteristics and a resultant ability to generate signal in optical imaging techniques while having the capability to degrade into inert particles of a size that can be readily cleared from the body via the kidney. The final specific aim was to determine whether the gold-coated liposomes of the second specific aim can serve as system for light-based delivery of an encapsulated agent in addition to its role as an optical contrast agent and its biodegradation capacity.Plasmon resonant nanorods and plasmon resonant gold-coated liposomes were generated by reducing free gold from solution onto surfactant coated seed particles and phospholipid liposomes, respectively. Both structures demonstrated the ability to generate signal in optical coherence tomography and in multi-photon confocal microscopy images. Nanorods in high intensity light demonstrate a capacity to mediate photo-thermal energy conversion. While, in similar conditions, gold-coated liposomes are shown to release their contents. Gold-coated liposomes are also shown to degrade to bioinert components of a size reasonable for rapid renal clearance using either surfactant or enzyme.