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

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 O₃ 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 O₃-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.