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Dual‐Mode Hybrid Discharge Plasma‐Activated Injectable Hydrosol for Enhanced Immunotherapeutic Cancer Therapy

Zewei WangFrontier Institute of Science and Technology Xi'an Jiaotong University Xi'an Shaanxi 710049 ChinaXixi JingState Key Laboratory of Electrical Insulation and Power Equipment Centre for Plasma Biomedicine Xi'an Jiaotong University Xi'an Shaanxi 710049 ChinaD ZhangState Key Laboratory of Electrical Insulation and Power Equipment Centre for Plasma Biomedicine Xi'an Jiaotong University Xi'an Shaanxi 710049 ChinaZhixiang YuFrontier Institute of Science and Technology Xi'an Jiaotong University Xi'an Shaanxi 710049 ChinaHao ZhangFrontier Institute of Science and Technology Xi'an Jiaotong University Xi'an Shaanxi 710049 ChinaDingxin LiuInterdisciplinary Research Center of Frontier Science and Technology Xi'an Jiaotong University Xi'an Shaanxi 710049 ChinaJishen ZhangInterdisciplinary Research Center of Frontier Science and Technology Xi'an Jiaotong University Xi'an Shaanxi 710049 ChinaYongping ShaoFrontier Institute of Science and Technology Xi'an Jiaotong University Xi'an Shaanxi 710049 ChinaMingzhe RongState Key Laboratory of Electrical Insulation and Power Equipment Centre for Plasma Biomedicine Xi'an Jiaotong University Xi'an Shaanxi 710049 ChinaMaksudbek YusupovInstitute of Fundamental and Applied Research National Research University TIIAME Kori Niyoziy 39 Tashkent 100000 UzbekistanFrancesco TampieriBiomaterials, Biomechanics and Tissue Engineering Group Department of Materials Science and Engineering and Institute for Research and Innovation in Health (IRIS) and Barcelona Research Centre in Multiscale Science and Engineering (CCEM) Universitat Politècnica de Catalunya – BarcelonaTech (UPC) Barcelona SpainPaul 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
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Abstract

Abstract Although cold atmospheric plasma is a promising therapeutic technique for tumor immunotherapy via reactive oxygen and nitrogen species (RONS), the challenges associated with the generation and delivery of these RONS hamper clinical adoption. Herein, a dual‐mode hybrid discharge plasma‐activated sodium alginate hydrosols (PAH SA ) is proposed to enhance the antitumor immune response. Gaseous highly reactive RONS are generated by dual‐mode hybrid plasma produced by mixed O 3 and NO x modes, which are converted into aqueous RONS in PAH SA via gas‐liquid reactions between plasma and hydrosols. In vitro results indicate that compared with O 3 ‐PAH SA and NO x ‐PAH SA , Hybrid‐PAH SA produces greater immunogenic cell death in cancer cells via the release of RONS. It also mediates the polarization of M2‐like macrophages to M1‐like macrophages to improve antitumor effects. In vivo studies confirm that Hybrid‐PAH SA inhibits B16F10 melanoma growth and produces stronger T‐cell‐mediated antitumor immune responses. Thus, Hybrid‐PAH SA offers a promising strategy for enhanced plasma‐induced cancer immunotherapy.

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