Bioactive Vanadium Disulfide Nanostructure with Dual Antitumor Effects of Vanadate and Gas for Immune-Checkpoint Blockade-Enhanced Cancer Immunotherapy

Bioactive inorganic nanomaterialsand the biologicaleffects ofmetal ions have attracted extensive attention in tumor therapy inrecent years. Vanadium (V), as a typical bioactive metal element,regulates a variety of biological functions. However, its role inantitumor therapy remains to be revealed. Herein, biodegradable vanadiumdisulfide (VS2) nanosheets (NSs) were prepared as a responsivegas donor and bioactive V source for activating cancer immunotherapyin combination with immune-checkpoint blockade therapy. After PEGylation,VS2-PEG exhibited efficient glutathione (GSH) depletionand GSH-activated hydrogen sulfide (H2S) release. ExogenousH(2)S caused lysosome escape and reduced adenosine triphosphate(ATP) synthesis in tumor cells by interfering with the mitochondrialmembrane potential and inducing acidosis. In addition, VS2-PEG degraded into high-valent vanadate, leading to Na+/K+ ATPase inhibition, potassium efflux, and interleukin(IL)-1 & beta; production. Together with further induction of ferroptosisand immunogenic cell death, a strong antitumor immune response wasstimulated by reversing the immunosuppressive tumor microenvironment.Moreover, the combined treatment of VS2-PEG and & alpha;-PD-1amplified antitumor therapy, significantly suppressed tumor growth,and further elicited robust immunity to effectively defeat tumors.This work highlights the biological effects of vanadium for applicationin cancer treatment.

Automated summary

Bioactive inorganic nanomaterials and the biological effects of metal ions have attracted extensive attention in tumor therapy. Vanadium, as a bioactive metal element, regulates various biological functions. However, its role in antitumor therapy still needs to be revealed.