Cytosolic delivery of the immunological adjuvant PolyⅠ:C and cytotoxic drug crystals via a carrier-free strategy significantly amplifies immune response  

作　　者：Xiaoqing Du Yuqi Hou Jia Huang Yan Pang Chenlu Ruan Wei Wu Chenjie Xu Hongwei Zhang Lifang Yin Wei He 

机构地区：[1]Department of Pharmaceutics,School of Pharmacy,China Pharmaceutical University,Nanjing 211198,China [2]Key Laboratory of Smart Drug Delivery of Ministry of Education of China,School of Pharmacy,Fudan University,Shanghai 201203,China [3]Department of Biomedical Engineering,City University of Hong Kong,Kowloon,Hong Kong SAR,China [4]Department of Pharmaceutical Sciences,School of Pharmacye Boston,MCPHS University,Boston,MA 02115,USA

出　　处：《Acta Pharmaceutica Sinica B》2021年第10期3272-3285,共14页药学学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Nos.81872823,81871477 and 82073782);the Double First-Class(CPU2018PZQ13,China)of the CPU;the Shanghai Science and Technology Committee(19430741500,China);the Key Laboratory of Modern Chinese Medicine Preparation of Ministry of Education of Jiangxi University of Traditional Chinese Medicine(TCM-201905,China)。

摘　　要：Co-delivery of chemotherapeutics and immunostimulant or chemoimmunotherapy is an emerging strategy in cancer therapy.The precise control of the targeting and release of agents is critical in this methodology.This article proposes the asynchronous release of the chemotherapeutic agents and immunostimulants to realize the synergistic effect between chemotherapy and immunotherapy.To obtain a proof-of-concept,a co-delivery system was prepared via a drug-delivering-drug(DDD)strategy for cytosolic co-delivery of Poly I:C,a synthetic ds RNA analog to activate RIG-I signaling,and PTX,a commonly used chemotherapeutics,in which pure PTX nanorods were sequentially coated with Poly I:C and mannuronic acid via stimulating the RIG-I signaling axis.The co-delivery system with a diameter of 200 nm enables profound immunogenicity of cancer cells,exhibiting increased secretion of cytokines and chemokines,pronounced immune response in vivo,and significant inhibition of tumor growth.Also,we found that intracellularly sustained release of cytotoxic agents could elicit the immunogenicity of cancer cells.Overall,the intracellular asynchronous release of chemotherapeutics and immunomodulators is a promising strategy to promote the immunogenicity of cancer cells and augment the antitumor immune response.

关 键 词：Asynchronous release CO-DELIVERY IMMUNOGENICITY Cancer cells IMMUNOSTIMULANT Paclitaxel CHEMOIMMUNOTHERAPY 

分 类 号：R730.51[医药卫生—肿瘤]