铜相关细胞死亡途径为肿瘤治疗带来了新的机遇。然而，在肿瘤中高效和有针对性地诱导铜相关细胞死亡仍然是一个挑战。不幸的是，众所周知的铜相关细胞死亡初始因子二硫化苯醚和铜络合物（DSF/Cu2+）也可以增加肿瘤中的PD-L1水平，这可能会降低最终的治疗效果。本研究中，DSF/Cu2+负载的MX烯纳米片被涂覆了PD-1过表达的T细胞膜以生成CuX-P系统。CuX-P可以像一块贴片一样识别和粘附于肿瘤细胞上的PD-L1，从而促进肿瘤细胞对CuX-P和PD-L1的内吞作用。随着DSF/Cu2+在细胞质中的内化和释放，PD-L1的表达增加。然而，由于肿瘤微环境中存在CuX-P，随后补充的PD-L1再次与CuX-P结合以进行内吞。这种反馈循环不断阻断和消耗肿瘤表面的PD-L1，并促进CuX-P在肿瘤中的富集以诱导铜相关细胞死亡。在激光照射下经过CuX-P处理后，三阴性乳腺癌小鼠模型中引发强烈的抗肿瘤免疫反应。因此，本研究开发了一种针对肿瘤的仿生系统，可实现同时的铜相关细胞死亡杀伤、光热治疗和免疫治疗。版权所有© 2023 Elsevier B.V.发表。

The cuproptosis cell death pathway brings fresh opportunities for tumor therapy. However, efficient and targeted cuproptosis induction in tumors is still a challenge. Unfortunately, the well-known cuproptosis initiator, disulfiram and copper complex (DSF/Cu2+), also increases PD-L1 level in tumors, which may diminish the final therapeutic outcome. In this study, DSF/Cu2+-loading MXene nanosheets are coated with PD-1 overexpressing T cell membrane to generate CuX-P system. CuX-P could recognize and stick to PD-L1 on tumor cells like a patch, which promotes the endocytosis of both CuX-P and PD-L1 by tumor cells. Following internalization and release of DSF/Cu2+ in the cytoplasm, PD-L1 expression is upregulated. However, due to the presence of CuX-P in the tumor microenvironment, the then supplemented PD-L1 on tumor surface again binds CuX-P for internalization. This feedback loop keeps blocking and consuming the PD-L1 on tumor surface and promotes the enrichment of CuX-P in tumors to induce cuproptosis. After CuX-P treatment with laser irradiation, strong anti-tumor immune responses are stimulated in a mouse model with triple-negative breast cancer. Thus, this study develops a tumor-targeted biomimetic system that offers simultaneous cuproptosis killing, photothermal therapy (PTT) and immunotherapy in mice.Copyright © 2023. Published by Elsevier B.V.