A critical challenge in photothermal therapy (PTT) remains in establishing systemic antitumor therapeutics against both primary and distant tumors, due to unsatisfactory photothermal conversion efficiency, insufficient tumor accumulation, and limited antitumor immunity of PTT agents. Here, outer membrane vesicles (OMVs) derived from Escherichia coli Nissle 1917 are explored as the nanoreactors to fabricate biomimetic copper sulfide nanoparticles (CuS-OMVs) for systemic photothermo-immunotherapeutic synergy. CuS-OMVs exhibit high photothermal conversion efficacy, good photostability, and considerable tumor targeting capacity, which thus cause apparent hyperthermia and subsequent distinct suppression of tumor cells at tumors upon second near-infrared (NIR-II) light irradiation. The CuS-OMVs-induced cytotoxicity elicits strong immunogenic cell death (ICD) of tumor cells, and facilitates dendritic cell (DC) maturation and consequent CD8⁺ T cell activation. Moreover, CuS-OMVs themselves are found to behave as immune adjuvants to promote DC maturation, and simultaneously repolarize M2-like tumor-associated macrophages (TAMs) into M1-like phenotype to reshape immunosuppressive tumor microenvironment. CuS-OMVs thus yield potent antitumor efficacies against both primary tumors and untreated distant tumors upon NIR-II light irradiation. This study provides insights into biomimetic nanomaterials for highly efficient photothermo-immunotherapy toward potent cancer therapy.

由于光热转换效率不理想、肿瘤积累不足以及 PTT 药物的抗肿瘤免疫力有限，光热疗法 (PTT) 的一个关键挑战仍然是建立针对原发性和远处肿瘤的系统性抗肿瘤疗法。在这里，来自大肠杆菌的外膜囊泡 (OMV)Nissle 1917 被探索为纳米反应器，用于制造仿生硫化铜纳米粒子 (CuS-OMV)，以实现系统性光热免疫治疗协同作用。CuS-OMVs表现出高光热转换效率、良好的光稳定性和相当大的肿瘤靶向能力，因此在第二次近红外（NIR-II）光照射下会导致明显的热疗和随后对肿瘤细胞的明显抑制。CuS-OMVs 诱导的细胞毒性引起肿瘤细胞的强烈免疫原性细胞死亡 (ICD)，并促进树突状细胞 (DC) 成熟和随后的 CD8 ⁺T细胞活化。此外，CuS-OMV 本身被发现可作为免疫佐剂促进 DC 成熟，同时将 M2 样肿瘤相关巨噬细胞 (TAM) 重新极化为 M1 样表型以重塑免疫抑制性肿瘤微环境。因此，CuS-OMV 在 NIR-II 光照射下对原发性肿瘤和未治疗的远处肿瘤均产生有效的抗肿瘤功效。这项研究提供了对用于高效光热免疫疗法的仿生纳米材料的见解，以实现有效的癌症治疗。