7-Dehydrocholesterol Encapsulated Polymeric Nanoparticles As a Radiation-Responsive Sensitizer for Enhancing Radiation Therapy
| Autor: | Ian Delahunty, Jianwen Li, Wen Jiang, Chaebin Lee, Xueyuan Yang, Anil Kumar, Zhi Liu, Weizhong Zhang, Jin Xie |
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| Rok vydání: | 2022 |
| Předmět: |
endocrine system
Radiation-Sensitizing Agents technology industry and agriculture General Chemistry Article Biomaterials Mice Dehydrocholesterols Polylactic Acid-Polyglycolic Acid Copolymer Cell Line Tumor Neoplasms Animals Nanoparticles General Materials Science Lactic Acid Polyglycolic Acid Biotechnology |
| Zdroj: | Small |
| ISSN: | 1613-6829 |
| Popis: | Therapeutics that can be activated by radiation in situ to enhance the efficacy of radiotherapy are highly desirable. Herein, 7-Dehydrocholesterol (7-DHC), a biosynthetic precursor of cholesterol, as a radiosensitizer, exploiting its ability to propagate the free radical chain reaction is explored. The studies show that 7-DHC can react with radiation-induced reactive oxygen species and in turn promote lipid peroxidation, double-strand breaks, and mitochondrial damage in cancer cells. For efficient delivery, 7-DHC is encapsulated into poly(lactic-co-glycolic acid) nanoparticles, forming 7-DHC@PLGA NPs. When tested in CT26 tumor bearing mice, 7-DHC@PLGA NPs significantly enhanced the efficacy of radiotherapy, causing complete tumor eradication in 30% of the treated animals. After treatment, 7-DHC is converted to cholesterol, causing no detectable side effects or hypercalcemia. 7-DHC@PLGA NPs represent a radiation-responsive sensitizer with great potential in clinical translation. |
| Databáze: | OpenAIRE |
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