PLGA Nanoparticles Loaded with Sorafenib Combined with Thermosensitive Hydrogel System and Microwave Hyperthermia for Multiple Sensitized Radiotherapy
Ziqi Wang,
Bo Liu,
Jingyao Tu,
Jingfeng Xiang,
Hui Xiong,
Yue Wu,
Shuaijie Ding,
Daoming Zhu,
Dongyong Zhu,
Fei Liu,
Guangyuan Hu,
Xianglin Yuan
Affiliations
Ziqi Wang
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Bo Liu
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Jingyao Tu
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Jingfeng Xiang
Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor and Department of General Surgery, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China
Hui Xiong
Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Yue Wu
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Shuaijie Ding
Department of Gastrointestinal Surgery and Department of Geriatrics, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, China
Daoming Zhu
Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor and Department of General Surgery, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China
Dongyong Zhu
Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Fei Liu
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Guangyuan Hu
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Xianglin Yuan
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
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.
