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 arti...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.展开更多
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+1 种基金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)。
文摘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.
