使用抗-PD-L1抗体偶联多功能纳米胶囊对癌症三阴性进行程序协同光化疗和免疫激活
Programmed Synergistic Photochemotherapy and Immune Activation of Triple Negative Breast Cancer Using Anti-PD-L1 Antibody-Conjugated Multifunctional Nanocapsules.
摘要(中文译文)
三阴性乳腺癌（TNBC）由于肿瘤微环境的免疫抑制状态以及相关抗原暴露有限，容易复发和转移，单纯化疗疗效不佳。我们开发了一种新型诊疗一体化纳米平台来解决这些问题：具有PD-L1介导金壳的多功能纳米胶囊（NCs）可诱导免疫原性细胞死亡（ICD）以重塑免疫微环境。PD-L1和NLG919双免疫检查点被编程为协同增敏光热治疗和化疗，并利用光声成像（PAI）对TNBC组织进行可视化和定位识别。采用改进的单乳化水包油（O/W）溶剂蒸发法、静电吸附法、金种子表面诱导结晶还原法和碳二亚胺法制备了DOX-NLG919@PLGA@Au-antiPD-L1 NCs（DNPA-aPD-L1 NCs）。建立了一系列动物模型，重点研究NCs的体内PAI、光化疗联合免疫治疗及抗肿瘤治疗效果、NCs诱导的ICD、NCs的代谢分布以及毒性试验。本项目成功构建了共载化疗药物多柔比星和吲哚胺2,3-双加氧酶抑制剂NLG919的PD-L1抗体修饰金纳米壳-PLGA核心NCs。激光触发的DOX、NLG919释放和光热治疗可协同诱导免疫原性细胞死亡（ICD），从而增强肿瘤免疫原性、抑制IDO并重塑肿瘤免疫微环境。这可有效消除原发性TNBC病灶，抑制复发和转移，显著延长荷瘤小鼠的生存期，且NCs具有良好的体内生物安全性。该诊断治疗剂可用于光化疗、免疫治疗和PAI，以实现对TNBC的可视化和识别。我们开发的DNPA-aPD-L1 NCs所介导的光化疗，结合肿瘤微环境重塑和免疫激活，在TNBC的诊断和治疗方面展现出巨大前景。
Abstract
Triple-negative breast cancer (TNBC) is prone to relapse and metastasis due to the immunosuppressive state of the tumor microenvironment and limited exposure to relevant antigens, and chemotherapy alone has poor efficacy. We have developed a novel theranostic nanoplatform to address these problems: multifunctional nanocapsules (NCs) with a PD-L1-mediated gold shell induce immunogenic cell death (ICD) to remodel the immune microenvironment. PD-L1 and NLG919 dual immune checkpoints are programmed to synergistically sensitize photothermal therapy and chemotherapy, and photoacoustic imaging (PAI) is used to visualize and localize TNBC tissues for identification. DOX-NLG919@PLGA@Au-antiPD-L1 NCs (DNPA-aPD-L1 NCs) were prepared using an improved single emulsion water-in-oil (O/W) solvent evaporation method, electrostatic adsorption, gold seed surface-induced crystallization reduction method, and carbodiimide method. A series of animal models were established to focus on the in vivo PAI of NCs, the effects of photochemotherapy combined with immunotherapy and antitumor therapy, ICD induced by NCs, the metabolic distribution of NCs, and toxicity tests. This project successfully constructed gold nanoshell-PLGA core NCs with PD-L1 antibody co-loaded with chemotherapeutic drugs doxorubicin and indoleamine 2,3-dioxygenase inhibitor NLG919. Laser-triggered release of DOX, NLG919, and photothermal therapy can synergistically induce immunogenic cell death (ICD), thereby enhancing tumor immunogenicity, inhibiting IDO, and reshaping the tumor immune microenvironment. This can effectively eliminate the primary TNBC lesions, inhibit recurrence and metastasis, significantly prolong the survival of tumor-bearing mice, and NCs have good in vivo biosafety. This diagnostic and therapeutic agent can be used for photochemotherapy, immunotherapy, and PAI to visualize and identify TNBC. The photochemotherapy mediated by the DNPA-aPD-L1 NCs we developed, combined with tumor microenvironment remodeling and immune activation, shows great promise for the diagnosis and treatment of TNBC.
如何引用
AMA
Zhiqiang Lin, Hui Jiang, Yingying Zhou, Li Xu, Lixin Jiang, Jing Du. Programmed Synergistic Photochemotherapy and Immune Activation of Triple Negative Breast Cancer Using Anti-PD-L1 Antibody-Conjugated Multifunctional Nanocapsules.. International journal of nanomedicine. 2026; doi:10.2147/IJN.S539732.
APA
Zhiqiang Lin, Hui Jiang, Yingying Zhou, Li Xu, Lixin Jiang, Jing Du (2026). Programmed Synergistic Photochemotherapy and Immune Activation of Triple Negative Breast Cancer Using Anti-PD-L1 Antibody-Conjugated Multifunctional Nanocapsules.. International journal of nanomedicine. https://doi.org/10.2147/IJN.S539732
GB/T 7714
Zhiqiang Lin, Hui Jiang, Yingying Zhou, Li Xu, Lixin Jiang, Jing Du. Programmed Synergistic Photochemotherapy and Immune Activation of Triple Negative Breast Cancer Using Anti-PD-L1 Antibody-Conjugated Multifunctional Nanocapsules.[J]. International journal of nanomedicine, 2026 doi:10.2147/IJN.S539732.
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