Employment of exosome-mimetic nanovesicles as a plasma adjuvant for cancer targeting through Golgi stress-associated ferroptosis

Plasma oncology is a promising therapeutic method that employs ionized gas to selectively target cancer cells. However, despite its efficacy in directly exposing external cancer cells to plasma, a stable delivery method through the circulatory system to internal cancer cells has yet to be developed. In this study, we revealed that bioinspired exosome-mimetic nanovesicles (EMs) can serve as a plasma adjuvant to enhance the anti-cancer effect. EM treatment increased the half-life of plasma reactive species such as nitrogen oxide in solution, thereby increasing the cytotoxicity towards cancer cells. Our syngeneic mice model experiment demonstrated that EM-treated plasma (EM-Plasma) inhibited in vivo cancer growth more efficiently than conventional plasma administration. Furthermore, we uncovered a molecular mechanism through which EM-Plasma selectively induces cancer cell death, namely, Golgi stress-associated ferroptosis. Our study provides a promising approach for the clinical application of plasma oncology in cancer treatment. Transcriptomic profiles of B16 melanoma cells with or without EM-Plasma treatment.