Bacterial and cancerous cell membrane fused liposome coordinates with PD-L1 inhibitor for cancer immunotherapy  

作　　者：Xianjin Luo Chenglong Li Zhaofei Guo Hairui Wang Penghui He Yuanhao Zhao Yi Lin Chunting He Yingying Hou Yongshun Zhang Guangsheng Du 

机构地区：[1]Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province,Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology,West China School of Pharmacy,Sichuan University,Chengdu 610064,China [2]Pharmaceutical Biotechnology,Department of Pharmacy,LMU Munich,Butenandt Strasse 5-13,Munich 81377,Germany [3]Department of Biomedical Engineering,College of Future Technology,Peking University,Beijing 100871,China

出　　处：《Nano Research》2024年第9期8389-8401,共13页纳米研究（英文版）

基　　金：supported by the National Natural Science Foundation of China(No.82341038);Natural Science Foundation of Sichuan Province(No.2022NSFSC1491);China Postdoctoral Science Foundation Grant(No.2019M663534,China);Sichuan Veterinary Medicine and Drug Innovation Group of China Agricultural Research System(CARS-SVIDIP);the Fundamental Research Funds for the Central Universities and Sichuan University Postdoctoral Interdisciplinary Innovation Fund.

摘　　要：Although tumor cell membranes with broad-spectrum antigens have been explored for cancer vaccines for decades,their relatively poor capacity to stimulate immune responses,especially cellular immune responses,has limited their application.Here,we presented a novel bacterial and cancerous cell membrane fusogenic liposome for co-delivering cell membrane-derived antigens and adjuvants.Meanwhile,a programmed death-ligand 1(PD-L1)inhibitor,JQ-1,was incorporated into the formulation to tackle the up-regulated PD-L1 expression of antigen-presenting cells(APCs)upon vaccination,thereby augmenting its anti-tumor efficacy.The fusogenic liposomes demonstrated significantly improved cellular uptake by APCs and effectively suppressed PD-L1 expression in bone marrow-derived dendritic cells(BMDCs)in vitro.Following subcutaneous vaccination,the nano-vaccines efficiently drained to the tumor-draining lymph nodes(TDLNs),and significantly inhibited PD-L1 expression of both dendritic cells(DCs)and macrophages within the TDLNs and tumors.As a result,the liposomal vaccine induced robust innate and cellular immune responses and inhibited tumor growth in a colorectal carcinoma-burden mouse model.In summary,the fabricated cell membrane-based fusogenic liposomes offer a safe,effective,and easily applicable strategy for tumor immunotherapy and hold potential for personalized cancer immunotherapy.

关 键 词：fusogenic liposome tumor cell membrane ADJUVANT programmed death-ligand 1(PD-L1)inhibitor tumor draining lymph nodes 

分 类 号：R730.51[医药卫生—肿瘤]