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载光敏剂和 Toll 样受体 7 激动剂的癌细胞膜包覆纳米颗粒用于增强联合肿瘤免疫治疗。

Cancer Cell Membrane-Coated Nanoparticle Co-loaded with Photosensitizer and Toll-like Receptor 7 Agonist for the Enhancement of Combined Tumor Immunotherapy.

机构信息

Guangdong Provincial Key Laboratory of New Drug Screening and NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, People's Republic of China.

Department of Musculoskeletal Oncology, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510642, Guangdong, People's Republic of China.

出版信息

ACS Nano. 2023 Sep 12;17(17):16620-16632. doi: 10.1021/acsnano.3c02724. Epub 2023 Aug 22.

DOI:10.1021/acsnano.3c02724
PMID:37606341
Abstract

Tumor immunotherapy has shown considerable therapeutic potential in the past few years, but the clinical response rate of immunotherapy is less than 20%. Encountering the high heterogeneity of tumors, it will be a general trend to apply combined therapy for cancer treatment. Photodynamic therapy (PDT) transiently kills tumor cells by producing reactive oxygen species (ROS), while residual tumor cells are prone to metastasis, leading to tumor recurrence. In combination with tumor immunotherapy, it is hoped to awaken the host immune system and eradicate residual tumor cells. Herein, cancer cell membrane-coated nanoparticles as a platform to combine PDT, TLR7 agonist, and tumor antigen for the enhancement of tumor therapeutic efficacy are designed. The final biomimetic nanoparticles (CCMV/LTNPs) can specifically kill tumor cells through PDT, while strong host antitumor immune responses are elicited to eliminate residue tumor cells under the help of immune adjuvant and tumor antigen from the cancer cell membrane. In summary, a photoimmunotherapy strategy is designed that synergistically enhances the tumor therapeutic effects by killing tumor cells through PDT and activating host antitumor immune responses through the co-delivery of adjuvant and tumor antigen, which may offer a promising strategy for clinical immunotherapy in the future.

摘要

肿瘤免疫疗法在过去几年中显示出了相当大的治疗潜力,但免疫疗法的临床反应率低于 20%。面对肿瘤的高度异质性,联合治疗将成为癌症治疗的一种趋势。光动力疗法(PDT)通过产生活性氧(ROS)来瞬时杀死肿瘤细胞,而残留的肿瘤细胞则容易转移,导致肿瘤复发。与肿瘤免疫疗法相结合,有望唤醒宿主免疫系统并清除残留的肿瘤细胞。在此,设计了一种以癌细胞膜包覆的纳米粒子作为平台,将 PDT、TLR7 激动剂和肿瘤抗原结合起来,以增强肿瘤治疗效果。最终的仿生纳米粒子(CCMV/LTNPs)可以通过 PDT 特异性地杀死肿瘤细胞,而在免疫佐剂和癌细胞膜上的肿瘤抗原的帮助下,会引发强烈的宿主抗肿瘤免疫反应,以清除残留的肿瘤细胞。总之,通过 PDT 杀死肿瘤细胞和通过共递呈佐剂和肿瘤抗原激活宿主抗肿瘤免疫反应的协同作用,设计了一种光免疫治疗策略,可显著增强肿瘤治疗效果,为未来的临床免疫治疗提供了一种有前景的策略。

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