Antioxidant Nanomedicine Significantly Enhances the Survival Benefit of Radiation Cancer Therapy by Mitigating Oxidative Stress-Induced Side Effects
Autor: | Ahram Kim, Chitho P. Feliciano, Yukio Nagasaki, Babita Shashni, Chiaki Yonemoto |
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Rok vydání: | 2021 |
Předmět: |
Programmed cell death
Antioxidant Necrosis Radioprotective Agent medicine.medical_treatment 02 engineering and technology Pharmacology 010402 general chemistry medicine.disease_cause 01 natural sciences Antioxidants Biomaterials Mice Neoplasms medicine Animals General Materials Science chemistry.chemical_classification Reactive oxygen species General Chemistry 021001 nanoscience & nanotechnology 0104 chemical sciences Radiation therapy Oxidative Stress Nanomedicine chemistry Apoptosis medicine.symptom 0210 nano-technology Reactive Oxygen Species Oxidative stress Biotechnology |
Zdroj: | Small (Weinheim an der Bergstrasse, Germany). 17(21) |
ISSN: | 1613-6829 |
Popis: | Oxidative stress-induced off-target effects limit the therapeutic window of radiation therapy. Although many antioxidants have been evaluated as radioprotective agents, none of them are in widespread clinical use, owing to the side effects of the antioxidants themselves and the lack of apparent benefit. Aiming for a truly effective radioprotective agent in radiation cancer therapy, the performance of a self-assembling antioxidant nanoparticle (herein denoted as redox nanoparticle; RNP) is evaluated in the local irradiation of a subcutaneous tumor-bearing mouse model. Since RNP is covered with a biocompatible shell layer and possesses a core-shell type structure of several tens of nanometers in size, its lifetime in the systemic circulation is prolonged. Moreover, since 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), one of the most potent antioxidants, is covalently encapsulated in the core of RNP, it exerts intense antioxidant activity and induces fewer adverse effects by avoiding leakage of the TEMPO molecules. Preadministration of RNP to the mouse model effectively mitigates side effects in normal tissues and significantly extends the survival benefit of radiation cancer therapy. Moreover, RNP pretreatment noticeably increases the apoptosis/necrosis ratio of radiation-induced cell death, a highly desirable property to reduce the chronic side effects of ionizing irradiation. |
Databáze: | OpenAIRE |
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