State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
School of Life Sciences, Hainan University, Haikou, 570228, China.
Angew Chem Int Ed Engl. 2022 Jul 4;61(27):e202202409. doi: 10.1002/anie.202202409. Epub 2022 May 9.
An approach of decorating bacteria with triple immune nanoactivators is reported to develop tumor-resident living immunotherapeutics. Under cytocompatible conditions, tumor-specific antigens and checkpoint blocking antibodies are simultaneously conjugated onto bacterial surface and then polydopamine nanoparticles are formed via in situ dopamine polymerization. In addition to serving as a linker, polydopamine with its photothermal effect can repolarize tumor-associated macrophages to a pro-inflammatory phenotype. The linked antigens promote the maturation of dendritic cells and generate tumor-specific immune responses, while the anchored antibodies block immune checkpoints and activate cytotoxic T lymphocytes. Decorated bacteria show spatiotemporal tumor retention and proliferation-dependent drug release, achieving potent antitumor effects in two antigen-overexpressing tumor models. This work provides a versatile platform to prepare multimodal and long-acting therapeutics for cancer immunotherapy.
一种用三重免疫纳米激活剂修饰细菌的方法被报道用于开发肿瘤驻留的活体免疫疗法。在细胞相容性条件下，将肿瘤特异性抗原和检查点阻断抗体同时偶联到细菌表面，然后通过原位多巴胺聚合形成聚多巴胺纳米粒子。除了作为连接物，具有光热效应的聚多巴胺可以将肿瘤相关巨噬细胞重新极化到促炎表型。连接的抗原促进树突状细胞的成熟并产生肿瘤特异性免疫反应，而锚定的抗体阻断免疫检查点并激活细胞毒性 T 淋巴细胞。修饰后的细菌表现出时空肿瘤保留和增殖依赖性药物释放，在两种抗原过表达的肿瘤模型中实现了强大的抗肿瘤效果。这项工作为制备用于癌症免疫治疗的多模式和长效治疗药物提供了一个通用平台。
