近年来，生物活性无机纳米材料和金属离子的生物效应在肿瘤治疗领域引起了广泛关注。作为一种典型的生物活性金属元素，钒（V）调节多种生物功能。然而，其在抗肿瘤治疗中的作用尚待揭示。本研究中，我们制备了可降解的二硫化钒（VS2）纳米片（NSs），作为敏感的气体供体和生物活性钒源，与免疫检查点阻断治疗联合激活癌症免疫治疗。经过PEG化，VS2-PEG显示出高效的谷胱甘肽（GSH）耗竭和GSH激活的硫化氢（H2S）释放。外源性H2S通过干扰线粒体膜电位和诱导酸中毒引起肿瘤细胞溶酶体逃逸和腺苷三磷酸（ATP）合成的降低。此外，VS2-PEG降解成高价钒酸盐，导致Na+/K+ ATP酶抑制、钾外流和白细胞介素（IL）-1β的产生。结合进一步诱导铁死亡和免疫原性细胞死亡，逆转免疫抑制的肿瘤微环境，刺激了强烈的抗肿瘤免疫应答。此外，VS2-PEG和α-PD-1的联合治疗放大了抗肿瘤疗效，显著抑制了肿瘤生长，并进一步激发了强大的免疫力以有效击败肿瘤。本研究突出了钒的生物效应，为其在癌症治疗中的应用提供了新的推动。

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.