Triple negative breast cancer (TNBC) exhibits limited responsiveness to immunotherapy owing to its immunosuppressive tumor microenvironment (TME). Here, a reactive oxygen species (ROS)-labile nanodrug encapsulating the photosensitizer Ce6 and Bcl-2 inhibitor ABT-737 was developed to provoke a robust immune response via the synergistic effect of photodynamic therapy (PDT) and the reversal of apoptosis resistance. Upon exposure to first-wave near-infrared laser irradiation, the generated ROS triggers PEG cleavage, facilitating the accumulation of the nanodrug at tumor region and endocytosis by tumor cells. Further irradiation leads to the substantial generation of cytotoxic ROS, initiating an immunogenic cell death (ICD) cascade, which prompts the maturation of dendritic cells (DCs) as well as the infiltration of T cells into the tumor site. Meanwhile, Bcl-2 inhibition counteracts apoptosis resistance, thereby amplifying PDT-induced ICD and bolstering antitumor immunity. As a result, the ROS-sensitive nanodrug demonstrates a potent inhibitory effect on tumor growth.

中文翻译：

---

光诱导纳米药物介导的光动力和抗凋亡协同作用增强三阴性乳腺癌免疫治疗

由于其免疫抑制肿瘤微环境（TME），三阴性乳腺癌（TNBC）对免疫治疗的反应有限。在这里，开发了一种封装光敏剂 Ce6 和 Bcl-2 抑制剂 ABT-737 的活性氧 (ROS) 不稳定纳米药物，通过光动力疗法 (PDT) 的协同效应和逆转细胞凋亡抵抗来激发强大的免疫反应。当暴露于第一波近红外激光照射时，产生的ROS触发PEG裂解，促进纳米药物在肿瘤区域的积累和肿瘤细胞的内吞作用。进一步的照射会导致细胞毒性 ROS 的大量产生，启动免疫原性细胞死亡 (ICD) 级联，从而促进树突状细胞 (DC) 的成熟以及 T 细胞浸润到肿瘤部位。同时，Bcl-2 抑制可抵消细胞凋亡抵抗，从而放大 PDT 诱导的 ICD 并增强抗肿瘤免疫。因此，ROS敏感的纳米药物对肿瘤生长具有有效的抑制作用。