基于二维（2D）纳米材料的催化肿瘤治疗是一种新兴且有前途的肿瘤治疗方式。然而，外源刺激的利用和转化效率低下，催化方式单一，肿瘤微环境（TME）中的治疗效果不理想，严重限制了其在肿瘤治疗中的进一步应用。在此，成功开发了名为T-HCN@CuMS的异质氮化碳基纳米制剂，极大地提高了肿瘤治疗方式的效率。受益于异质氮化碳纳米片（HCN）内的供体-受体（三嗪-庚嗪）结构以及铜负载金属二硫化钼纳米片（CuMS）的面间异质结构的构建，T-HCN@CuMS呈现出良好的光诱导催化作用在近红外（NIR）光照射下产生丰富的活性氧（ROS）的特性。此外，CuMS的选择同时使该纳米剂能够有效催化类芬顿反应并触发细胞铜凋亡，这是一种最近公认的调节细胞死亡模式，其特征是细胞内铜稳态失衡和脂酰化线粒体蛋白聚集。此外，通过cRGDfk-PEG2k-DSPE进行表面修饰，制备了T-HCN@CuMS，并赋予其改善的分散性和αvβ3整合素靶向能力。总的来说，通过合理的设计，T-HCN@CuMS易于制备，并且在体外和高转移原位骨肉瘤模型中均取得了令人满意的抗肿瘤和抗转移结果。该策略可以为基于二维纳米材料治疗恶性疾病提供一种思路。

Catalytic tumor therapy based on two-dimensional (2D) nanomaterials is a burgeoning and promising tumor therapeutic modality. However, the inefficient utilization and conversion of exogenous stimulation, single catalytic modality, and unsatisfactory therapeutic efficiency in the tumor microenvironment (TME) have seriously restricted their further application in tumor therapy. Herein, the heterogeneous carbon nitride-based nanoagent named T-HCN@CuMS was successfully developed, which dramatically improved the efficiency of the tumor therapeutic modality. Benefiting from the donor-acceptor (triazine-heptazine) structure within the heterogeneous carbon nitride nanosheets (HCN) and the construction of interplanar heterostructure with copper loaded metallic molybdenum bisulfide nanosheets (CuMS), T-HCN@CuMS presented a favorable photo-induced catalytic property to generate abundant reactive oxygen species (ROS) under near-infrared (NIR) light irradiation. Besides, the choice of CuMS simultaneously enabled this nanoagent to efficiently catalyze the Fenton-like reaction and trigger cell cuproptosis, a recently recognized regulated cell death mode characterized by imbalanced intracellular copper homeostasis and aggregation of lipoylated mitochondrial proteins. Moreover, upon surface modification with cRGDfk-PEG2k-DSPE, T-HCN@CuMS was prepared and endowed with improved dispersibility and αvβ3 integrins targeting ability. In general, through the rational design, T-HCN@CuMS was facilely prepared and had achieved satisfactory antitumor and antimetastasis outcomes both in vitro and in a high-metastatic orthotopic osteosarcoma model. This strategy could offer an idea to treat malignant diseases based on 2D nanomaterials.