An antigen self-assembled and dendritic cell-targeted nanovaccine for enhanced immunity against cancer  

作　　者：Yunting Zhang Min Jiangy Guangsheng Du Xiaofang Zhong Chunting He Ming Qin Yingying Hou Rong Liu Xun Sun 

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 610041,China

出　　处：《Acta Pharmaceutica Sinica B》2023年第8期3518-3534,共17页药学学报(英文版)

基　　金：financially supported by the National Natural Science Foundation of China(81925036&81872814);the Key Research and Development Program of Science and Technology Department of Sichuan Province(2020YFS0570,China);Sichuan Veterinary Medicine and Drug Innovation Group of China Agricultural Research System(CARS-SVDIP);111 project(b18035,China);the Fundamental Research Funds for the Central Universities(China)。

摘　　要：The rise of nanotechnology has opened new horizons for cancer immunotherapy.However,most nano vaccines fabricated with nanomaterials suffer from carrier-related concerns,including low drug loading capacity,unpredictable metabolism,and potential systemic toxicity,which bring obstacles for their clinical translation.Herein,we developed an antigen self-assembled nanovaccine,which was resulted from a simple acryloyl modification of the antigen to induce self-assembly.Furthermore,a dendritic cell targeting head mannose monomer and a mevalonate pathway inhibitor zoledronic acid(Zol)were integrated or absorbed onto the nanoparticles(denoted as MEAO-Z)to intensify the immune response.The synthesized nano vaccine with a diameter of around 70 nm showed successful lymph node transportation,high dendritic cell internalization,promoted costimulatory molecule expression,and preferable antigen cross-presentation.In virtue of the above superiorities,MEAO-Z induced remarkably higher titers of serum antibody,stronger cytotoxic T lymphocyte immune responses and IFN-γsecretion than free antigen and adjuvants.In vivo,MEAO-Z significantly suppressed EG7-OVA tumor groth and prolonged the survival time of tumor-bearing mice.These results indicated the translation promise of our self-assembled nano vaccine for immune potentiation and cancer immunotherapy.

关 键 词：Subunit antigen Self-assembled nanovaccine Dendritic cell Mannose receptor Zoledronic acid Antigen cross-presentation Cellular immunity Cancer immunotherapy 

分 类 号：R73[医药卫生—肿瘤]