Hypoxic microenvironment and glutathione (GSH) accumulation in tumours limit the efficacy of cytotoxic reactive oxygen species (ROS) anti-tumour therapy. To address this challenge, we increased the consumption of GSH and the production of ROS through a novel nanoplatform with the action of inorganic nanoenzymes. In this study, we prepared mesoporous FeS₂ using a simple template method, efficiently loaded AIPH, and assembled Ti₃C₂/FeS₂-AIPH@BSA (TFAB) nanocomposites through self-assembly with BSA and 2D Ti₃C₂. The constructed TFAB nanotherapeutic platform enhanced chemodynamic therapy (CDT) by generating toxic hydroxyl radicals (˙OH) via FeS₂, while consuming GSH to reduce the loss of generated ˙OH via glutathione oxidase-like (GSH-OXD). In addition, TFAB is able to stimulate the decomposition of AIPH under 808 nm laser irradiation to produce oxygen-independent biotoxic alkyl radicals (˙R) for thermodynamic therapy (TDT). In conclusion, TFAB represents an innovative nanoplatform that effectively addresses the limitations of free radical-based treatment strategies. Through the synergistic therapeutic strategy of photothermal therapy (PTT), CDT, and TDT within the tumor microenvironment, TFAB nanoplatforms achieve controlled AIPH release, ROS generation, intracellular GSH consumption, and precise temperature elevation, resulting in enhanced intracellular oxidative stress, significant apoptotic cell death, and notable tumor growth inhibition. This comprehensive treatment strategy shows great promise in the field of tumor therapy.

中文翻译：

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FeS2 改性 MXene 纳米复合材料平台，通过增强 GSH 消耗实现高效 PTT/CDT/TDT 集成

肿瘤中的缺氧微环境和谷胱甘肽（GSH）积累限制了细胞毒性活性氧（ROS）抗肿瘤治疗的功效。为了应对这一挑战，我们通过具有无机纳米酶作用的新型纳米平台增加了 GSH 的消耗和 ROS 的产量。在本研究中，我们采用简单的模板方法制备了介孔FeS _{2 ，高效负载AIPH，并通过BSA和2D Ti 3} C ₂自组装组装了Ti ₃ C ₂ /FeS ₂ -AIPH@BSA (TFAB)纳米复合材料。构建的TFAB纳米治疗平台通过FeS 2_产生有毒的羟基自由基(˙OH)，同时消耗GSH以减少通过类谷胱甘肽氧化酶(GSH-OXD)产生的˙OH的损失，从而增强化学动力学治疗(CDT)。此外，TFAB能够在808 nm激光照射下刺激AIPH分解，产生不依赖氧的生物毒性烷基自由基（˙R），用于热力学治疗（TDT）。总之，TFAB 代表了一种创新的纳米平台，可以有效解决基于自由基的治疗策略的局限性。通过光热疗法（PTT）、CDT和TDT在肿瘤微环境中的协同治疗策略，TFAB纳米平台实现了受控的AIPH释放、ROS生成、细胞内GSH消耗和精确的温度升高，导致细胞内氧化应激增强，细胞凋亡显着死亡，并显着抑制肿瘤生长。这种综合治疗策略在肿瘤治疗领域显示出巨大的前景。