Abstract
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.
基金项目
广东省自然科学基金(2023A1515030291)
Science and Technol-ogy Program of Guangzhou(202201011130280065)
国家自然科学基金(82172079)
Special Fund of Foshan Climbing Peak Plan(2020B018)
NETL
NSTL
万方数据