Violet phosphorene nanosheets and cold atmospheric plasma for synergetic cancer therapy

Violet phosphorene nanosheets (VPNS), another type of two-dimensional nonmetal nanostructure, is a promising nanomaterial for biomedical applications. Cold atmospheric plasma (CAP) is an emerging anti-cancer strategy. Here, for the first time, a synergistic combination of VPNS and CAP exhibited remarkable efficacy in cancer treatment. Our findings revealed that VPNS and CAP effectively suppress cancer cell viability by inhibiting cell proliferation and inducing cell apoptosis in vitro. Moreover, we demonstrated the synergistic anti-cancer effect of VPNS and CAP in vivo, with low or no side effects. By metabolism analysis in vivo, we first reported that VPNS-1 inhibited tumor growth by down-regulating Delta-12-Prostaglandin J2, 8,9-DiHETrE, and Hepoxilin B, thereby suppressing arachidonic acid metabolism. Additionally, the down-regulation of AKT and anti-apoptotic proteins (Bcl-2, Bcl-xL and Mcl-1) of Bcl-2 family contributed to the inhibition of cell growth and the initiation of cell apoptosis. Our results unveiled a novel and promising anti-cancer approach involving the combined treatment of VPNS and CAP.