Visualizable Delivery of Nanodisc Antigen-Conjugated Adjuvant for Cancer Immunotherapy  

作　　者：Yangyun Wang Subin Lin Hanqiu Jiang Yuan Gu Yanxian Wu Jie Ma Yubin Ke Leshuai W.Zhang Yong Wang Mingyuan Gao 

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 215123 [2]Department of Orthopedic,The Second Affiliated Hospital of Soochow University,Suzhou 215004 [3]China Spallation Neutron Source,Dongguan Branch,Institute of High Energy Physics,Chinese Academy of Sciences,Dongguan 523803 [4]Institute of Chemistry,Chinese Academy of Sciences,Beijing 100190

出　　处：《CCS Chemistry》2022年第4期1238-1250,共13页中国化学会会刊（英文）

基　　金：supported by National Natural Science Foundation of China(nos.21874097 and 12075164);National Key Research Program of China(no.2018YFA0208800);Suzhou Administration of Science and Technology(no.sys2018021);Jiangsu Province’s Natural Science Foundation(no.SBK2020041529);Pre-Research Foundation of the Second Affiliated Hospital of Soochow University(no.SDFEYBS1906);the Scientific Research Program for Young Talents of China National Nuclear Corporation;A Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD);the support by the Youth Innovation Promotion Association,Chinese Academy of Sciences(no.2020010).

摘　　要：Engineering synthetic vaccines is promising for improving the efficacy of cancer immunotherapy.One of the major challenges in the development of vaccines is achieving controllable codelivery of antigen and adjuvant to lymph nodes for maximizing the antitumor immune responses.To address this issue,we herein developed an innovative visualizable nanodisc vaccine based on ovalbumin(OVA)and short-stranded oligodeoxynucleotides containing unmethylated cytosine-phosphate-guanine(CpG)motifs.The nanovaccine was fabricated by covalently attaching CpG onto the surface of a nanodisc antigen formed upon self-assembly of amphiphilic molecular conjugates of OVA and cypate(Cy),a near-infrared(NIR)fluorescent dye,for noninvasively visualizing the delivery of the resulting nanovaccines.Systematic in vitro experiments demonstrated that the engineered nanovaccines can specifically locate to dendritic cells(DCs)via toll-like receptor 9 and membrane thiols,and then efficiently activate DCs.The animal experiments combining NIR fluorescence imaging with the lymphatic T-cell phenotype and key cytokine secretion analyses revealed that targeted lymphatic homing of the mature DCs and consequent priming of CD8^(+)T cells were enabled to initiate strong tumor-specific T-cell responses with robust immune memory effects.Thus,this study offers a visualizable platform for optimizing the efficacy of nanovaccines toward cancer immunotherapies.

关 键 词：nanovaccines DC activation in vivo trafficking visualization IMMUNOTHERAPY 

分 类 号：O48[理学—固体物理]