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Bacterial Membrane Vesicles as Heteroantigen Reservoirs for Potentiated Colorectal Cancer Immunotherapy

文献类型：期刊论文

作者Liu, Chang6,7,8; Yang, Canyu3,7,8; Jiang, Xiuxian6,7,8; Lu, Xiang5; Huang, Xiaoyu5; Wei, Junchao4,7,8; Nie, Di6,7,8; Wang, Yang4,7,8; Guo, Shiyan6,7,8; Zheng, Ying1
刊名ACS NANO
出版日期2025-06-26
卷号19期号:26页码:23760-23777
关键词immunotherapy bacterial membrane vesicle heteroantigen reservoir PD-L1 siRNA immune checkpointblockade
ISSN号1936-0851
DOI10.1021/acsnano.5c03862
英文摘要Cancer immunotherapy, including immune checkpoint blockade (ICB), often has limited efficacy due to inadequate neoantigen exposure. Although neoantigen vaccines can enhance immune sensitization, their clinical application is hindered by high identification costs and tumor heterogeneity. Alternatively, heteroantigen presentation by cancer cells offers a promising strategy to improve immunotherapy. Herein, hyaluronic acid (HA)-modified bacterial membrane vesicles were developed as heteroantigen reservoirs (HLGV) and then further loaded with PD-L1 siRNA (siPD-L1) for immune checkpoint blockade. Intracellularly, HLGV released heteroantigens and siPD-L1 into the cytoplasm via early endosomal membrane fusion. The heteroantigens were presented by MHC class I molecules, while siPD-L1 escaped lysosomal degradation and effectively silenced PD-L1 expression. When administered peritumorally, the synergistic therapeutic effect of heteroantigen presentation and ICB significantly inhibited both subcutaneous CT-26 tumors and distant metastases. For colorectal cancer immunotherapy, HLGV@siPD-L1 was encapsuled into chondroitin sulfate hydrogel microspheres (HEBV@siPD-L1) and administered through oral gavage. Ultimately, HEBV@siPD-L1 increased the infiltration of macrophages and CD8+ T cells and effectively suppressed the growth of orthotopic colorectal cancer, with the tumor inhibition rate reaching 91.6%. These findings demonstrated the potential of bacterial membrane vesicles as heteroantigen reservoirs to activate antitumor immune responses, which could further synergize with ICB for promoted immune efficacy.
WOS关键词IMMUNE CHECKPOINT INHIBITORS ; T-CELLS ; RECOGNITION
资助项目National Natural Science Foundation of China[82025032] ; National Natural Science Foundation of China[82430111] ; National Natural Science Foundation of China[82304392] ; National Natural Science Foundation of China[NCTIB2022HS01006] ; National Natural Science Foundation of China[CASIMM0120232002] ; National Natural Science Foundation of China[SIMM0220232001] ; Self Designed Scientific Research of Shanghai Institute of Materia Medica, Chinese Academy of Sciences[23HC1401200] ; Shanghai Action Plan for Science, Technology and Innovation[2021M703350] ; China Postdoctoral Science Foundation[2021427] ; China Postdoctoral Science Foundation[2022693] ; Shanghai Postdoctoral Excellence Program
WOS研究方向Chemistry ; Science & Technology - Other Topics ; Materials Science
语种英语
WOS记录号WOS:001518562000001
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/318669]  
专题新药研究国家重点实验室
通讯作者Pan, Chao; Gan, Yong
作者单位1.Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macau 999078, Peoples R China
2.Natl Inst Food & Drug Control, NMPA Key Lab Qual Res & Evaluat Pharmaceut Excipie, Beijing 100050, Peoples R China
3.Shenyang Pharmaceut Univ, Sch Pharm, Shenyang 110016, Peoples R China
4.Henan Univ, Sch Pharm, Kaifeng 475004, Peoples R China
5.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210046, Peoples R China
6.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
7.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China
8.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Liu, Chang,Yang, Canyu,Jiang, Xiuxian,et al. Bacterial Membrane Vesicles as Heteroantigen Reservoirs for Potentiated Colorectal Cancer Immunotherapy[J]. ACS NANO,2025,19(26):23760-23777.
APA Liu, Chang.,Yang, Canyu.,Jiang, Xiuxian.,Lu, Xiang.,Huang, Xiaoyu.,...&Gan, Yong.(2025).Bacterial Membrane Vesicles as Heteroantigen Reservoirs for Potentiated Colorectal Cancer Immunotherapy.ACS NANO,19(26),23760-23777.
MLA Liu, Chang,et al."Bacterial Membrane Vesicles as Heteroantigen Reservoirs for Potentiated Colorectal Cancer Immunotherapy".ACS NANO 19.26(2025):23760-23777.

入库方式： OAI收割

来源：上海药物研究所

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