A rationally designed cancer vaccine based on NIR-II fluorescence image-guided light-triggered remote control of antigen cross-presentation and autophagy

作     者：Aihua Wu Afeng Yang Qinli Tong Guoguang Wei Sihang Zhang Sheng Yu Chen Zhang Jiaojiao Xu Wei Lu Aihua Wu;Afeng Yang;Qinli Tong;Guoguang Wei;Sihang Zhang;Sheng Yu;Chen Zhang;Jiaojiao Xu;Wei Lu

作者机构：School of Pharmacy&Minhang HospitalKey Laboratory of Smart Drug DeliveryMinistry of Education&State Key Laboratory of Molecular Engineering of PolymersFudan UniversityShanghai 201203China 

出 版 物：《药学学报:英文版》 (Acta Pharmaceutica Sinica B)

年 卷 期：2023年第13卷第7期

页      面：3121-3136页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 100705[医学-微生物与生化药学] 1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported in part by grants from National Natural Science Foundation of China(No.81991493,China) Shanghai Municipal Health Commission(No.2022XD045,China) 

主　　题：Vaccine Light-triggered NIR-II imaging Cross-presentation Autophagy Simvastatin Endolysosomal escape Dendritic cell maturation 

摘      要：Cancer vaccines represent a promising immunotherapeutic treatment *** promotion of cross-presentation of extracellular tumor-associated antigens on the major histocompatibility complex(MHC) class I molecules and dendritic cell maturation at the appropriate time and place is crucial for cancer vaccines to prime cytolytic T cell response with reduced side *** vaccination strategies,however,are not able to achieve the spatiotemporal control of antigen ***,we report a liposomal vaccine loading the second near-infrared window(NIR-II,1000—1700 nm) fluorophore BPBBT with an efficient photothermal conversion effect that offers an NIR-light-triggered endolysosomal escape under the imaging *** NIR-II image-guided vaccination strategy specifically controls the cytosolic delivery of antigens for cross-presentation in the draining lymph nodes(DLNs).Moreover,the photothermally induced endolysosomal rupture initiates *** also find that the adjuvant simvastatin acts as an autophagy activator through inhibiting the PI3K/AKT/m TOR *** light-induced autophagy in the DLNs together with simvastatin treatment cooperatively increase MHC class II expression by activating autophagy machinery for dendritic cell *** study presents a paradigm of NIR-II image-guided light-triggered *** approach for remote control of antigen cross-presentation and autophagy represents a new strategy for vaccine development.