Zhang Jinzha, Shi Mingkang, Sun Jiawen, Xu Lingxia, Xu Yuping, Jiang Wentao, Zhao Wenbo, Zhou Min, Mao Chun, Zhang Shirong
National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China.
Department of Vascular Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University, Nanjing 210008, China.
ACS Appl Mater Interfaces. 2025 Jan 29;17(4):5735-5751. doi: 10.1021/acsami.4c16568. Epub 2025 Jan 17.
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.
纳米技术的可设计性和高反应活性为通过调节肿瘤细胞中的氧化还原状态进行抗肿瘤治疗提供了策略。在此，我们合成了一种包裹在牛血清白蛋白中且含有二硫键的二氧化钒纳米颗粒（VSB NPs），用于光热增强铁死亡和焦亡效应。机制研究表明，二硫键可有效消耗肿瘤微环境中过表达的谷胱甘肽（GSH），导致谷胱甘肽过氧化物酶4（GPX4）活性降低。同时，四价钒可诱导过表达的HO发生催化反应，产生大量有毒的羟基自由基（·OH）和单线态氧（O），导致肿瘤细胞铁死亡。此外，二硫键的消耗还可导致纳米颗粒降解为高价钒酸盐，激活热蛋白结构域相关蛋白3（NLRP3）炎性小体并引起肿瘤细胞焦亡。值得一提的是，VSB NPs不仅可在近红外光照射下消融肿瘤细胞，还可进一步破坏肿瘤微环境的氧化还原稳态，从而增强可生物降解的钒基纳米材料诱导的肿瘤细胞铁死亡和焦亡。这种基于钒的生物学效应来调节肿瘤细胞氧化还原状态的策略为癌症治疗提供了可能性。
