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PLGA Nanoparticles Loaded with Sorafenib Combined with Thermosensitive Hydrogel System and Microwave Hyperthermia for Multiple Sensitized Radiotherapy

Hypoxia is typically the leading cause of radiotherapy (RT) resistance in solid tumors, and glutathione (GSH) overexpression in tumor cells is a potent antioxidant mechanism that protects tumor cells from radiation damage. Herein, we developed a sorafenib (SFN) loaded-PLGA hydrogel system (SPH) in c...

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Autores principales: Wang, Ziqi, Liu, Bo, Tu, Jingyao, Xiang, Jingfeng, Xiong, Hui, Wu, Yue, Ding, Shuaijie, Zhu, Daoming, Zhu, Dongyong, Liu, Fei, Hu, Guangyuan, Yuan, Xianglin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9965455/
https://www.ncbi.nlm.nih.gov/pubmed/36839808
http://dx.doi.org/10.3390/pharmaceutics15020487
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author Wang, Ziqi
Liu, Bo
Tu, Jingyao
Xiang, Jingfeng
Xiong, Hui
Wu, Yue
Ding, Shuaijie
Zhu, Daoming
Zhu, Dongyong
Liu, Fei
Hu, Guangyuan
Yuan, Xianglin
author_facet Wang, Ziqi
Liu, Bo
Tu, Jingyao
Xiang, Jingfeng
Xiong, Hui
Wu, Yue
Ding, Shuaijie
Zhu, Daoming
Zhu, Dongyong
Liu, Fei
Hu, Guangyuan
Yuan, Xianglin
author_sort Wang, Ziqi
collection PubMed
description Hypoxia is typically the leading cause of radiotherapy (RT) resistance in solid tumors, and glutathione (GSH) overexpression in tumor cells is a potent antioxidant mechanism that protects tumor cells from radiation damage. Herein, we developed a sorafenib (SFN) loaded-PLGA hydrogel system (SPH) in combination with microwave (MW) hyperthermia for RT sensitization. SPH with stable properties was produced by combining SFN and PLGA in a specific ratio and encapsulating the mixture in agarose hydrogel. Intratumoral injection of SPH to mice combined with MW hyperthermia can not only directly cause thermal damage to tumor cells, but also increase blood oxygen delivery to the tumor site, thus overcoming the problem of intratumoral hypoxia and achieving “first layer” RT sensitization. Moreover, high temperatures can cause the hydrogel to disintegrate and release SFN. Not only can SFN inhibit tumor growth, but it can also achieve the “second layer” of RT sensitization by inhibiting glutathione (GSH) synthesis in cells and increasing reactive oxygen species (ROS) production. Experiments, both in vitro and in vivo, have indicated that SPH and MW hyperthermia can achieve a double RT sensitization effect and a significant tumor inhibition effect. In conclusion, combining our SPH nanosystem and thermoradiotherapy is a promising anti-tumor treatment.
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spelling pubmed-99654552023-02-26 PLGA Nanoparticles Loaded with Sorafenib Combined with Thermosensitive Hydrogel System and Microwave Hyperthermia for Multiple Sensitized Radiotherapy Wang, Ziqi Liu, Bo Tu, Jingyao Xiang, Jingfeng Xiong, Hui Wu, Yue Ding, Shuaijie Zhu, Daoming Zhu, Dongyong Liu, Fei Hu, Guangyuan Yuan, Xianglin Pharmaceutics Article Hypoxia is typically the leading cause of radiotherapy (RT) resistance in solid tumors, and glutathione (GSH) overexpression in tumor cells is a potent antioxidant mechanism that protects tumor cells from radiation damage. Herein, we developed a sorafenib (SFN) loaded-PLGA hydrogel system (SPH) in combination with microwave (MW) hyperthermia for RT sensitization. SPH with stable properties was produced by combining SFN and PLGA in a specific ratio and encapsulating the mixture in agarose hydrogel. Intratumoral injection of SPH to mice combined with MW hyperthermia can not only directly cause thermal damage to tumor cells, but also increase blood oxygen delivery to the tumor site, thus overcoming the problem of intratumoral hypoxia and achieving “first layer” RT sensitization. Moreover, high temperatures can cause the hydrogel to disintegrate and release SFN. Not only can SFN inhibit tumor growth, but it can also achieve the “second layer” of RT sensitization by inhibiting glutathione (GSH) synthesis in cells and increasing reactive oxygen species (ROS) production. Experiments, both in vitro and in vivo, have indicated that SPH and MW hyperthermia can achieve a double RT sensitization effect and a significant tumor inhibition effect. In conclusion, combining our SPH nanosystem and thermoradiotherapy is a promising anti-tumor treatment. MDPI 2023-02-01 /pmc/articles/PMC9965455/ /pubmed/36839808 http://dx.doi.org/10.3390/pharmaceutics15020487 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Ziqi
Liu, Bo
Tu, Jingyao
Xiang, Jingfeng
Xiong, Hui
Wu, Yue
Ding, Shuaijie
Zhu, Daoming
Zhu, Dongyong
Liu, Fei
Hu, Guangyuan
Yuan, Xianglin
PLGA Nanoparticles Loaded with Sorafenib Combined with Thermosensitive Hydrogel System and Microwave Hyperthermia for Multiple Sensitized Radiotherapy
title PLGA Nanoparticles Loaded with Sorafenib Combined with Thermosensitive Hydrogel System and Microwave Hyperthermia for Multiple Sensitized Radiotherapy
title_full PLGA Nanoparticles Loaded with Sorafenib Combined with Thermosensitive Hydrogel System and Microwave Hyperthermia for Multiple Sensitized Radiotherapy
title_fullStr PLGA Nanoparticles Loaded with Sorafenib Combined with Thermosensitive Hydrogel System and Microwave Hyperthermia for Multiple Sensitized Radiotherapy
title_full_unstemmed PLGA Nanoparticles Loaded with Sorafenib Combined with Thermosensitive Hydrogel System and Microwave Hyperthermia for Multiple Sensitized Radiotherapy
title_short PLGA Nanoparticles Loaded with Sorafenib Combined with Thermosensitive Hydrogel System and Microwave Hyperthermia for Multiple Sensitized Radiotherapy
title_sort plga nanoparticles loaded with sorafenib combined with thermosensitive hydrogel system and microwave hyperthermia for multiple sensitized radiotherapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9965455/
https://www.ncbi.nlm.nih.gov/pubmed/36839808
http://dx.doi.org/10.3390/pharmaceutics15020487
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