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

Wang, Zewei; Jing, Xixi; Zhang, Danqi; Yu, Zimu; Zhang, Hao; Liu, Dingxin; Zhang, Jishen; Shao, Yongping et al. · Adv Healthc Mater · 2026

basic_science · Level V

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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<sub>SA</sub>) is proposed to enhance the antitumor immune response. Gaseous highly reactive RONS are generated by dual-mode hybrid plasma produced by mixed O<sub>3</sub> and NO<sub>x</sub> modes, which are converted into aqueous RONS in PAH<sub>SA</sub> via gas-liquid reactions between plasma and hydrosols. In vitro results indicate that compared with O<sub>3</sub>-PAH<sub>SA</sub> and NO<sub>x</sub>-PAH<sub>SA</sub>, Hybrid-PAH<sub>SA</sub> 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<sub>SA</sub> inhibits B16F10 melanoma growth and produces stronger T-cell-mediated antitumor immune responses. Thus, Hybrid-PAH<sub>SA</sub> offers a promising strategy for enhanced plasma-induced cancer immunotherapy.

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