DataSheet_1_Injectable Hydrogel System for Camptothecin Initiated Nanocatalytic Tumor Therapy With High Performance.docx

Single photothermal therapy (PTT) has many limitations in tumor treatments. Multifunctional nanomaterials can cooperate with PTT to achieve profound tumor killing performance. Herein, we encapsulated chemotherapeutic drug camptothecin (CPT) and pyrite (FeS2) with dual enzyme activity (glutathione oxidase (GSH-OXD) and peroxidase (POD) activities) into an injectable hydrogel to form a CFH system, which can improve the level of intratumoral oxidative stress, and simultaneously realize FeS2-mediated PTT and nanozymes catalytic treatment. After laser irradiation, the hydrogel gradually heats up and softens under the photothermal agent FeS2. The CPT then released from CFH to tumor microenvironment (TME), thereby enhancing the H2O2 level. As a result, FeS2 can catalyze H2O2 to produce ·OH, and cooperate with high temperature to achieve high-efficiency tumor therapy. It is worth noting that FeS2 can also deplete excess glutathione (GSH) in the cellular level, further amplifying oxidative stress. Both in vivo and in vitro experiments show that our CFH exhibits good tumor-specific cytotoxicity. The CFH we developed provides new insights for tumor treatment.

单一光热治疗（PTT）在肿瘤治疗中存在诸多局限。多功能纳米材料可与光热治疗协同，实现高效的肿瘤杀伤效果。在此研究中，我们将化疗药物喜树碱（CPT）与具备双酶活性（谷胱甘肽氧化酶（GSH-OXD）及过氧化物酶（POD）活性）的黄铁矿（FeS₂）封装至可注射水凝胶中，构建得到CFH体系。该体系可提升瘤内氧化应激水平，同时实现FeS₂介导的光热治疗与纳米酶催化治疗。经激光辐照后，水凝胶在光热剂FeS₂的作用下逐渐升温并软化，CPT随之从CFH体系释放至肿瘤微环境（TME），进而提高过氧化氢（H₂O₂）水平。借此，FeS₂可催化H₂O₂生成羟基自由基（·OH），并与高温协同实现高效肿瘤治疗。值得注意的是，FeS₂还可在细胞层面消耗过量的谷胱甘肽（GSH），进一步放大氧化应激效应。体内外实验均证实，我们开发的CFH体系展现出良好的肿瘤特异性细胞毒性。本研究构建的CFH体系为肿瘤治疗提供了全新的研究思路。