Department of Biotherapy, Huaxi MR Research Center (HMRRC), Day Surgery Center, Department of Radiology, Cancer Center, Research Core Facilities of West China Hospital, National Clinical Research Center for Geriatrics, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
Amgen Bioprocessing Centre, Keck Graduate Institute, Claremont, CA, 91711, USA.
Adv Sci (Weinh). 2022 Aug;9(22):e2201734. doi: 10.1002/advs.202201734. Epub 2022 Jun 2.
Tumor immunotherapy is only effective in a fraction of patients due to a low response rate and severe side effects, and these challenges of immunotherapy in clinics can be addressed through induction of immunogenic cell death (ICD). ICD is elicited from many antitumor therapies to release danger associated molecular patterns (DAMPs) and tumor-associated antigens to facilitate maturation of dendritic cells (DCs) and infiltration of cytotoxic T lymphocytes (CTLs). The process can reverse the tumor immunosuppressive microenvironment to improve the sensitivity of immunotherapy. Nanostructure-based drug delivery systems (NDDSs) are explored to induce ICD by incorporating therapeutic molecules for chemotherapy, photosensitizers (PSs) for photodynamic therapy (PDT), photothermal conversion agents for photothermal therapy (PTT), and radiosensitizers for radiotherapy (RT). These NDDSs can release loaded agents at a right dose in the right place at the right time, resulting in greater effectiveness and lower toxicity. Immunotherapeutic agents can also be combined with these NDDSs to achieve the synergic antitumor effect in a multi-modality therapeutic approach. In this review, NDDSs are harnessed to load multiple agents to induce ICD by chemotherapy, PDT, PTT, and RT in combination of immunotherapy to promote the therapeutic effect and reduce side effects associated with cancer treatment.
肿瘤免疫疗法由于反应率低和严重的副作用,仅在一部分患者中有效,而这些免疫疗法在临床上的挑战可以通过诱导免疫原性细胞死亡(ICD)来解决。ICD 可以从许多抗肿瘤治疗中引发,以释放危险相关分子模式(DAMPs)和肿瘤相关抗原,从而促进树突状细胞(DCs)的成熟和细胞毒性 T 淋巴细胞(CTLs)的浸润。这一过程可以逆转肿瘤免疫抑制微环境,提高免疫疗法的敏感性。目前正在探索基于纳米结构的药物递送系统(NDDS),通过将化疗治疗分子、光动力疗法(PDT)的光敏剂(PS)、光热疗法(PTT)的光热转换剂和放射疗法(RT)的放射增敏剂等治疗分子整合到其中,来诱导 ICD。这些 NDDS 可以在适当的时间和地点以适当的剂量释放负载的药物,从而提高疗效,降低毒性。免疫治疗剂也可以与这些 NDDS 联合使用,以实现多模态治疗方法中的协同抗肿瘤作用。在这篇综述中,我们利用 NDDS 来负载多种药物,通过化疗、PDT、PTT 和 RT 联合免疫疗法诱导 ICD,以促进治疗效果并降低与癌症治疗相关的副作用。
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