Littérature scientifique sur le sujet « Carboranes Therapeutic use »

Magnetic Fe3O4 nanoparticles (NPs) and their surface modification with therapeutic substances are of great interest, especially drug delivery for cancer therapy, including boron-neutron capture therapy (BNCT). In this paper, we present the results of boron-rich compound (carborane borate) attachment to previously aminated by (3-aminopropyl)-trimethoxysilane (APTMS) iron oxide NPs. Fourier transform infrared spectroscopy with Attenuated total reflectance accessory (ATR-FTIR) and energy-dispersive X-ray analysis confirmed the change of the element content of NPs after modification and formation of new bonds between Fe3O4 NPs and the attached molecules. Transmission (TEM) and scanning electron microscopy (SEM) showed Fe3O4 NPs’ average size of 18.9 nm. Phase parameters were studied by powder X-ray diffraction (XRD), and the magnetic behavior of Fe3O4 NPs was elucidated by Mössbauer spectroscopy. The colloidal and chemical stability of NPs was studied using simulated body fluid (phosphate buffer—PBS). Modified NPs have shown excellent stability in PBS (pH = 7.4), characterized by XRD, Mössbauer spectroscopy, and dynamic light scattering (DLS). Biocompatibility was evaluated in-vitro using cultured mouse embryonic fibroblasts (MEFs). The results show us an increasing of IC50 from 0.110 mg/mL for Fe3O4 NPs to 0.405 mg/mL for Fe3O4-Carborane NPs. The obtained data confirm the biocompatibility and stability of synthesized NPs and the potential to use them in BNCT.

The development of methods for targeted delivery of payload is a rapidly developing area of research.For this reason, iron oxide nanoparticles have potential to be used in delivery of substances by using external magnetic field. However it is necessary to develop methods of their modification, which will lead to the pos-sibility of immobilization of payloads with the required concentration for therapeutic use. In this article, supermagnetic iron oxide nanoparticles (Fe3O4) were modified with silanes such as (3-chloropropyl)-trimethoxysilane, (3-mercaptopropyl)trimethoxysilane, (3-aminopropyl)trimethoxysilane and (3-glycidyl-propyl)trimethoxysilane by reaction of polycondensation. Then carborane compound (payload) was success-fully attached on the modified nanoparticles via covalent bonding. Structure, size and element composition were studied by Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and Energy-dispersive X-ray spectroscopy (EDA). It was found that resulting nanoparticles contain 16.6% of bo-ron (according to EDA), and their average size is 32±9 nm (according to SEM). In vitro test using HeLa (cer-vical cancer cell) and PC-3 (prostate cancer cell) shows low cytotoxicity in concentration range of 1–200μg/ml.

A boronated analogue of the antiestrogen U 23,469-M (D. Lednicer, D. W. Emmert, S. C. Lyster, and G. W. Duncan, J. Med. Chem . 12, 881 (1969)) was prepared, for possible use in neutron capture therapy of estrogen receptor-positive tumors. In this analogue, the terminal OH group was replaced by a B-decachloro-o-carboranyl residue. This com pound showed a large, non-specific uptake in ZR75-1 breast cancer-derived cells. It could partially inhibit the uptake of estradiol in these cells. Accumulation in the cells at physiologically obtainable concentrations was, however, too low to envisage a therapeutic effect following thermal neutron irradiation.

"January 2004"
Bibliography: leaves 163-184.
v, 184 leaves : ill. (some col.), photos ; 30 cm.
Title page, contents and abstract only. The complete thesis in print form is available from the University Library.
Thesis (Ph.D.)--University of Adelaide, School of Chemistry and Physics, Discipline of Chemistry, 2004