Photo-manipulated polyunsaturated fatty acid-doped liposomal hydrogel for flexible photoimmunotherapy  

作　　者：Xinyue Lan Junguang Liang Churan Wen Xiaolong Quan Huimin Lin Qinqin Xu Peixian Chen Guangyu Yao Dan Zhou Meng Yu 

机构地区：[1]Breast Center,Department of General Surgery,Nanfang Hospital,Southern Medical University,Guangzhou 510515,China [2]NMPA Key Laboratory for Research and Evaluation of Drug Metabolism&Guangdong Provincial Key Laboratory of New Drug Screening,School of Pharmaceutical Sciences,Southern Medical University,Guangzhou 510515,China [3]Department of Breast Surgery,The First People's Hospital of Foshan,Foshan 528100,China [4]Zhujiang Hospital,Southern Medical University,Guangzhou 510282,China

出　　处：《Chinese Chemical Letters》2024年第4期268-274,共7页中国化学快报（英文版）

基　　金：supported by the Natural Science Foundation of Guangdong Province (No.2023A1515030291);Science and Technology Program of Guangzhou (No.202201011130280065);National Natural Science Foundation of China (No.82172079);Special Fund of Foshan Climbing Peak Plan (No.2020B018)。

摘　　要：Despite the synergy of immune checkpoint blockade(ICB) therapy and photodynamic therapy(PDT) holds great promise as countermeasures against breast cancer, exploring long-term or flexible short-time therapeutic strategies in “cold” tumors remains a great challenge. Here, we present a polyunsaturated fatty acid-doped liposomal hydrogel Lp(DHA)@CP Gel loaded with photosensitizer chlorin e6(Ce6) and programmed death-ligand 1 antibody(αPD-L1) for flexible local photoimmunotherapy with merely singledosed administration. The presence of polyunsaturated fatty acid(docosahexaenoic acid, DHA) doped in particle membrane endows liposomes with flexibly reactive oxygen species(ROS)-responsive release capability, which was attributed to the presence of abundant unsaturated groups. The αPD-L1 was repeatedly induced to in situ release in response to the PDT under photo-exposure. The immunogenic cell death(ICD) effect of PDT evoked “cold” breast tumor to “hot” one, and then assisted the cascade releasedαPD-L1 to synergistically boost the immunotherapy. After a single dose of peritumoral administration of Lp(DHA)@CP Gel, the on-demand treatment can maximize patient compliance and safety by adjusting therapeutic behaviors via a photo on-off switch. This work presents a flexible medication platform,showing promise in improving the objective response rate of ICB therapy and minimizing its systemic toxicity.

关 键 词：Photodynamic therapy IMMUNOTHERAPY Responsive release Immunogenic cell death Liposomal hydrogel 

分 类 号：R318.08[医药卫生—生物医学工程] TQ427.26[医药卫生—基础医学]