Cytosolic delivery of the immunological adjuvant Poly I: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
• 来源期刊: 药学学报（英文版）
• 年，卷（期）: 2021,（10）
• 所属期刊栏目: Original articles
• 页码范围: 3272-3285
• 页数: 14页
• 语种: 英文

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 dsRNA 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 can-cer 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.