Cargando…

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

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 immunost...

Descripción completa

Detalles Bibliográficos
Autores principales: Du, Xiaoqing, Hou, Yuqi, Huang, Jia, Pang, Yan, Ruan, Chenlu, Wu, Wei, Xu, Chenjie, Zhang, Hongwei, Yin, Lifang, He, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8546930/
https://www.ncbi.nlm.nih.gov/pubmed/34729315
http://dx.doi.org/10.1016/j.apsb.2021.03.014
_version_ 1784590284820054016
author Du, Xiaoqing
Hou, Yuqi
Huang, Jia
Pang, Yan
Ruan, Chenlu
Wu, Wei
Xu, Chenjie
Zhang, Hongwei
Yin, Lifang
He, Wei
author_facet Du, Xiaoqing
Hou, Yuqi
Huang, Jia
Pang, Yan
Ruan, Chenlu
Wu, Wei
Xu, Chenjie
Zhang, Hongwei
Yin, Lifang
He, Wei
author_sort Du, Xiaoqing
collection PubMed
description 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 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.
format Online
Article
Text
id pubmed-8546930
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-85469302021-11-01 Cytosolic delivery of the immunological adjuvant Poly I:C and cytotoxic drug crystals via a carrier-free strategy significantly amplifies immune response Du, Xiaoqing Hou, Yuqi Huang, Jia Pang, Yan Ruan, Chenlu Wu, Wei Xu, Chenjie Zhang, Hongwei Yin, Lifang He, Wei Acta Pharm Sin B Original Article 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 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. Elsevier 2021-10 2021-03-12 /pmc/articles/PMC8546930/ /pubmed/34729315 http://dx.doi.org/10.1016/j.apsb.2021.03.014 Text en © 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Du, Xiaoqing
Hou, Yuqi
Huang, Jia
Pang, Yan
Ruan, Chenlu
Wu, Wei
Xu, Chenjie
Zhang, Hongwei
Yin, Lifang
He, Wei
Cytosolic delivery of the immunological adjuvant Poly I:C and cytotoxic drug crystals via a carrier-free strategy significantly amplifies immune response
title Cytosolic delivery of the immunological adjuvant Poly I:C and cytotoxic drug crystals via a carrier-free strategy significantly amplifies immune response
title_full Cytosolic delivery of the immunological adjuvant Poly I:C and cytotoxic drug crystals via a carrier-free strategy significantly amplifies immune response
title_fullStr Cytosolic delivery of the immunological adjuvant Poly I:C and cytotoxic drug crystals via a carrier-free strategy significantly amplifies immune response
title_full_unstemmed Cytosolic delivery of the immunological adjuvant Poly I:C and cytotoxic drug crystals via a carrier-free strategy significantly amplifies immune response
title_short Cytosolic delivery of the immunological adjuvant Poly I:C and cytotoxic drug crystals via a carrier-free strategy significantly amplifies immune response
title_sort cytosolic delivery of the immunological adjuvant poly i:c and cytotoxic drug crystals via a carrier-free strategy significantly amplifies immune response
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8546930/
https://www.ncbi.nlm.nih.gov/pubmed/34729315
http://dx.doi.org/10.1016/j.apsb.2021.03.014
work_keys_str_mv AT duxiaoqing cytosolicdeliveryoftheimmunologicaladjuvantpolyicandcytotoxicdrugcrystalsviaacarrierfreestrategysignificantlyamplifiesimmuneresponse
AT houyuqi cytosolicdeliveryoftheimmunologicaladjuvantpolyicandcytotoxicdrugcrystalsviaacarrierfreestrategysignificantlyamplifiesimmuneresponse
AT huangjia cytosolicdeliveryoftheimmunologicaladjuvantpolyicandcytotoxicdrugcrystalsviaacarrierfreestrategysignificantlyamplifiesimmuneresponse
AT pangyan cytosolicdeliveryoftheimmunologicaladjuvantpolyicandcytotoxicdrugcrystalsviaacarrierfreestrategysignificantlyamplifiesimmuneresponse
AT ruanchenlu cytosolicdeliveryoftheimmunologicaladjuvantpolyicandcytotoxicdrugcrystalsviaacarrierfreestrategysignificantlyamplifiesimmuneresponse
AT wuwei cytosolicdeliveryoftheimmunologicaladjuvantpolyicandcytotoxicdrugcrystalsviaacarrierfreestrategysignificantlyamplifiesimmuneresponse
AT xuchenjie cytosolicdeliveryoftheimmunologicaladjuvantpolyicandcytotoxicdrugcrystalsviaacarrierfreestrategysignificantlyamplifiesimmuneresponse
AT zhanghongwei cytosolicdeliveryoftheimmunologicaladjuvantpolyicandcytotoxicdrugcrystalsviaacarrierfreestrategysignificantlyamplifiesimmuneresponse
AT yinlifang cytosolicdeliveryoftheimmunologicaladjuvantpolyicandcytotoxicdrugcrystalsviaacarrierfreestrategysignificantlyamplifiesimmuneresponse
AT hewei cytosolicdeliveryoftheimmunologicaladjuvantpolyicandcytotoxicdrugcrystalsviaacarrierfreestrategysignificantlyamplifiesimmuneresponse