Abstract

Bioactive inorganic nanomaterials and the biological effects of metal ions have attracted extensive attention in tumor therapy in recent years. Vanadium (V), as a typical bioactive metal element, regulates a variety of biological functions. However, its role in antitumor therapy remains to be revealed. Herein, biodegradable vanadium disulfide (VS2) nanosheets (NSs) were prepared as a responsive gas donor and bioactive V source for activating cancer immunotherapy in combination with immune-checkpoint blockade therapy. After PEGylation, VS2-PEG exhibited efficient glutathione (GSH) depletion and GSH-activated hydrogen sulfide (H2S) release. Exogenous H2S caused lysosome escape and reduced adenosine triphosphate (ATP) synthesis in tumor cells by interfering with the mitochondrial membrane potential and inducing acidosis. In addition, VS2-PEG degraded into high-valent vanadate, leading to Na+/K+ ATPase inhibition, potassium efflux, and interleukin (IL)-1β production. Together with further induction of ferroptosis and immunogenic cell death, a strong antitumor immune response was stimulated by reversing the immunosuppressive tumor microenvironment. Moreover, the combined treatment of VS2-PEG and α-PD-1 amplified antitumor therapy, significantly suppressed tumor growth, and further elicited robust immunity to effectively defeat tumors. This work highlights the biological effects of vanadium for application in cancer treatment.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.