Biomimetic Tumor Cell Membrane‐Encapsulated Nanoparticles Combine NIR‐II Photothermal Therapy and Chemotherapy for Enhanced Immunotherapy in Triple‐Negative Breast Cancer

Abstract To advance the understanding and potential treatment strategies for triple‐negative breast cancer (TNBC), particularly focusing on its high metastatic propensity and uncertain molecular targets, a biomimetic tumor cell membrane‐encapsulated nanodelivery system is developed for enhanced immunotherapy. This system is assembled with the second near‐infrared (NIR‐II) photothermal agent, chemotherapeutic drug, and programmed death‐ligand 1 (PD‐L1) inhibitors camouflaged by TNBC cell membranes. An NIR‐II Ag 2 S quantum dots (QDs) is introduced for not only realizing pronounced imaging‐guided photothermal therapy (PTT), but also co‐activating immunogenic cell death (ICD) with chemotherapy. Homologous targeting and camouflage properties endowed the nanodelivery system with excellent biocompatibility and efficient delivery ability to the tumor site, demonstrating excellent synergistic therapeutic efficacy. The release of damage‐associated molecular patterns (DAMP) marked the induction of ICD, crucial for reshaping the immune microenvironment. Further integration of α‐PD‐L1 achieved a 56.5% immune checkpoint inhibition rate, synergistically amplifying immune response to ultimately activate key cytokines, thereby achieving pronounced anti‐tumor immunotherapy effects. Notably, this approach realized a considerable reduction of metastatic nodules by 51.2% in the TNBC lung metastasis model. The proposed nanodelivery system extended tumor remission and effectively reduced lung metastasis, paving the way for a reliable and promising approach in TNBC immunotherapy.

摘要：为了增进对三阴性乳腺癌（TNBC）的理解和潜在的治疗策略，特别是关注其高转移倾向和不确定的分子靶点，开发了一种仿生肿瘤细胞膜封装的纳米递送系统用于增强免疫治疗。该系统由第二近红外 (NIR-II) 光热剂、化疗药物和通过 TNBC 细胞膜伪装的程序性死亡配体 1 (PD-L1) 抑制剂组装而成。引入 NIR-II Ag 2 S 量子点（QD）不仅可以实现显着的成像引导光热疗法（PTT），而且可以与化疗共同激活免疫原性细胞死亡（ICD）。同源靶向和伪装特性赋予纳米递送系统优异的生物相容性和高效到达肿瘤部位的递送能力，表现出优异的协同治疗功效。损伤相关分子模式 (DAMP) 的释放标志着 ICD 的诱导，这对于重塑免疫微环境至关重要。 α-PD-L1的进一步整合实现了56.5%的免疫检查点抑制率，协同放大免疫反应，最终激活关键细胞因子，从而达到显着的抗肿瘤免疫治疗效果。值得注意的是，这种方法在 TNBC 肺转移模型中实现了转移结节显着减少 51.2%。所提出的纳米递送系统延长了肿瘤缓解并有效减少了肺转移，为 TNBC 免疫治疗中可靠且有前景的方法铺平了道路。