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

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外文摘要：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 ther-apeutic 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 pro-grammed death-ligand 1 antibody(αPD-L1)for flexible local photoimmunotherapy with merely single-dosed 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 re-peatedly 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 adjust-ing 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.

外文关键词：

Photodynamic therapyImmunotherapyResponsive releaseImmunogenic cell deathLiposomal hydrogel

作者：

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

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作者单位：

Breast Center,Department of General Surgery,Nanfang Hospital,Southern Medical University,Guangzhou 510515,China

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

Department of Breast Surgery,The First People's Hospital of Foshan,Foshan 528100,China

Zhujiang Hospital,Southern Medical University,Guangzhou 510282,China

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基金：

广东省自然科学基金Science and Technol-ogy Program of Guangzhou国家自然科学基金Special Fund of Foshan Climbing Peak Plan

项目编号：

2023A1515030291202201011130280065821720792020B018

出版年：

2024

DOI：

10.1016/j.cclet.2023.108616

中国化学快报(英文版)