Biodegradable Vanadium-Based Nanomaterials for Photothermal-Enhanced Tumor Ferroptosis and Pyroptosis.

The designability and high reactivity of nanotechnology provide strategies for antitumor therapy by regulating the redox state in tumor cells. Here, we synthesize a kind of vanadium dioxide nanoparticle encapsulated in bovine serum albumin and containing disulfide bonds (VSB NPs) for photothermal-enhanced ferroptosis and pyroptosis effects. Mechanism studies show that disulfide bonds can effectively consume overexpressed glutathione (GSH) in the tumor microenvironment, leading to a decrease in glutathione peroxidase 4 (GPX4) activity. Simultaneously, tetravalent vanadium can induce a catalytic reaction of overexpressed HO, producing plenty of toxic hydroxyl radicals (·OH) and singlet oxygen (O), leading to tumor cell ferroptosis. In addition, the consumption of disulfide bonds can also lead to the degradation of nanoparticles into high-valent vanadates, activating thermal protein domain-associated protein 3 (NLRP3) inflammasomes and causing tumor cell pyroptosis. It is worth mentioning that VSB NPs can not only ablate tumor cells under near-infrared light irradiation but also further disrupt the redox homeostasis of the tumor microenvironment, thereby enhancing the ferroptosis and pyroptosis of tumor cells induced by biodegradable vanadium-based nanomaterials. This strategy, based on the biological effects of vanadium to regulate the redox state in tumor cells, provides possibilities for cancer treatment.