Therapeutic dendritic cell vaccines engineered with antigen-biomineralized Bi_(2)S_(3) nanoparticles for personalized tumor radioimmunotherapy  

作　　者：Huan Yu Haoxiang Guo He Zu Heng Ding Subin Lin Yangyun Wang Leshuai W Zhang Yong Wang 

机构地区：[1]State Key Laboratory of Radiation Medicine and Protection,School of Radiation Medicine and Protection,Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions,Soochow University,Suzhou,China [2]Department of Orthopedic,The Second Affiliated Hospital of Soochow University,Suzhou,China

出　　处：《Aggregate》2022年第5期227-237,共11页聚集体（英文）

基　　金：National Natural Science Foundation of China,Grant/Award Numbers:22122407,12175162,32171403,12075164,31971319,21874097;National Key Research Program of China,Grant/Award Number:2018YFA0208800;Tang Scholar Program;Scientific Research Program for Young Talents of China National Nuclear Corporation and A Priority Academic Program Development of Jiangsu Higher Education Institutions。

摘　　要：Therapeutic vaccines,an exciting development in cancer immunotherapy,share the goal of priming of personalized antigen-specific T-cell response by precise antigen presentation of dendritic cells(DCs),but major obstacles include insufficient antigen loading and off-target to DCs remain to their success.Here,we developed an imageable therapeutic vaccine with whole-antigen loading and target delivery constructed by ovalbumin(OVA)-biomineralized Bi_(2)S_(3) nanoparticles-pulsed DCs.Relying on the strong X-ray absorption and fluorescence labeling performance of Bi_(2)S_(3)@OVA nanoparticles,the in vivo spatiotemporal fate of the vaccine(Bi_(2)S_(3)@OVA@DC)can be noninvasively monitored by computed tomography and near-infrared fluorescence imaging in real time.The Bi_(2)S_(3)@OVA@DC can rapidly and durably accumulate in draining lymph nodes and thus trigger stronger T-cell responses compared to OVA-pulsed DCs.Meanwhile,Bi_(2)S_(3)@OVA@DC can further achieve in vivo antitumor effects against OVA-expressing B16F10 melanoma when combined with fractionated radiotherapy,resulting from the upregulation of cytotoxic CD8^(+)T cells and restraint of regulatory T cells in the tumor microenvironment,and the systemical secretion of OVA-specific IgG1/IgG2α antibody.Overall,we successfully fabricated an engineered DC vaccine featured in high whole-antigen loading capacity that can be precisely delivered to the lymphatic system for visualization,serving as a powerful therapeutic platform for cancer radioimmunotherapy.

关 键 词：antigen-biomineralized Bi_(2)S_(3)nanoparticles dendritic cells RADIOIMMUNOTHERAPY therapeutic vaccines visualization 

分 类 号：R730.51[医药卫生—肿瘤]