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Synergistic anticancer effects of plasma-activated hydrogel and CuMOF by inducing hybrid oxidative stress

Zewei WangFrontier Institute of Science and Technology, Xi’an Jiaotong University, Xi’an, ChinaZimu YuFrontier Institute of Science and Technology, Xi’an Jiaotong University, Xi’an, ChinaXixi JingCenter for Plasma Biomedicine, State Key Laboratory of Electrical Insulation and Power Equipment, Xi’an Jiaotong University, Xi’an, ChinaDanqi ZhangFrontier Institute of Science and Technology, Xi’an Jiaotong University, Xi’an, ChinaYuqi WangFrontier Institute of Science and Technology, Xi’an Jiaotong University, Xi’an, ChinaJishen ZhangCenter for Plasma Biomedicine, State Key Laboratory of Electrical Insulation and Power Equipment, Xi’an Jiaotong University, Xi’an, ChinaHao ZhangFrontier Institute of Science and Technology, Xi’an Jiaotong University, Xi’an, ChinaYi HuDepartment of Burns, The First Affiliated Hospital of Anhui Medical University, Hefei, ChinaO. A. KovalInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Akad. Lavrentiev Ave. 8, Novosibirsk, RussiaMaksudbek YusupovInstitute of Fundamental and Applied Research, National Research University TIIAME, Kori Niyoziy 39, Tashkent, UzbekistanJamoliddin RazzokovInstitute of Fundamental and Applied Research, National Research University TIIAME, Kori Niyoziy 39, Tashkent, UzbekistanDingxin LiuCenter for Plasma Biomedicine, State Key Laboratory of Electrical Insulation and Power Equipment, Xi’an Jiaotong University, Xi’an, ChinaZimu XuSchool of Resources and Environmental Engineering, Hefei University of Technology, Hefei, PR ChinaXiaolin ZhangDepartment of Physics, Department of Materials Science and Engineering, and Department of Biomedical Engineering, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, ChinaChengbiao DingDepartment of Physics, Department of Materials Science and Engineering, and Department of Biomedical Engineering, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, ChinaPaul K ChuDepartment of Physics, Department of Materials Science and Engineering, and Department of Biomedical Engineering, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, China
ABI

Аннотация

Although cold atmospheric plasma-activated hydrogel (PAH) loaded with plasma-generated reactive oxygen and nitrogen species (RONS) exhibits significant anticancer potential arising from slow RONS release, challenges, such as low RONS delivery efficiency, remain. The copper metal-organic framework (CuMOF), a new class of nanomaterials, induces the accumulation of reactive oxygen species (ROS), leading to apoptosis. Herein, a plasma-activated Pluronic F127 hydrogel (PAH<sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">PF127</sub>) is prepared by air discharge plasma to synergize with CuMOF for enhanced anticancer effects. The PAH<sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">PF127</sub> can load, store, and slow-release various RONS species generated by plasma. The plasma treatment does not adversely affect the temperature sensitivity, injectability, absorbance, or rheological properties of the Pluronic F127 hydrogel. In vitro studies reveal that PAH<sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">PF127</sub> induces oxidative stress, leading to B16F10 melanoma cell death by lowering cell viability and increasing intracellular ROS levels. In contrast, the introduction of oxidative stress mediated by PAH<sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">PF127</sub> in cancer cells is significantly greater when the hydrogel is used in combination with CuMOF compared to when it is used alone. In vivo results demonstrate that the synergy of PAHPF127 and Cu-MOF elicits a pronounced synergistic anticancer efficacy. The PAH<sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">PF127</sub>-CuMOF markedly attenuates neoplastic proliferation while concomitantly inducing higher cell apoptosis and excellent biosafety. The findings suggest that combining PAH with novel nanomaterials is a promising approach to enhance the anticancer efficacy and offers a new strategy for cancer therapy.

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