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Amplifying STING Activation by Cyclic Dinucleotide-Manganese Particles for Local and Systemic Cancer Metalloimmunotherapy

Nutritional metal ions play critical roles in many important immune processes. Hence, effective modulation of metal ions may open up new forms of immunotherapy, termed as metalloimmunotherapy. Here, we demonstrate a prototype of cancer metalloimmunotherapy using cyclic dinucleotide (CDN) stimulator...

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Autores principales: Sun, Xiaoqi, Zhang, Yu, Li, Jiaqian, Park, Kyung Soo, Han, Kai, Zhou, Xingwu, Xu, Yao, Nam, Jutaek, Xu, Jin, Shi, Xiaoyue, Wei, Lei, Lei, Yu Leo, Moon, James J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8595610/
https://www.ncbi.nlm.nih.gov/pubmed/34594005
http://dx.doi.org/10.1038/s41565-021-00962-9
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author Sun, Xiaoqi
Zhang, Yu
Li, Jiaqian
Park, Kyung Soo
Han, Kai
Zhou, Xingwu
Xu, Yao
Nam, Jutaek
Xu, Jin
Shi, Xiaoyue
Wei, Lei
Lei, Yu Leo
Moon, James J.
author_facet Sun, Xiaoqi
Zhang, Yu
Li, Jiaqian
Park, Kyung Soo
Han, Kai
Zhou, Xingwu
Xu, Yao
Nam, Jutaek
Xu, Jin
Shi, Xiaoyue
Wei, Lei
Lei, Yu Leo
Moon, James J.
author_sort Sun, Xiaoqi
collection PubMed
description Nutritional metal ions play critical roles in many important immune processes. Hence, effective modulation of metal ions may open up new forms of immunotherapy, termed as metalloimmunotherapy. Here, we demonstrate a prototype of cancer metalloimmunotherapy using cyclic dinucleotide (CDN) stimulator of interferon genes (STING) agonists and Mn(2+). We screened various metal ions and discovered specific metal ions augmented STING agonist activity, wherein Mn(2+) promoted a 12- to 77-fold potentiation effect across the prevalent human STING haplotypes. Notably, Mn(2+) coordinated with CDN STING agonists to self-assemble into a nanoparticle (CDN-Mn(2+) particle, CMP) that effectively delivered STING agonists to immune cells. CMP administered either by local intratumoral or systemic intravenous injection initiated robust anti-tumor immunity, achieving remarkable therapeutic efficacy with minute doses of STING agonists in multiple murine tumor models. Overall, CMP offers a new platform for local and systemic cancer treatments, and this work underscores the great potential of coordination nanomedicine for metalloimmunotherapy.
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spelling pubmed-85956102022-03-30 Amplifying STING Activation by Cyclic Dinucleotide-Manganese Particles for Local and Systemic Cancer Metalloimmunotherapy Sun, Xiaoqi Zhang, Yu Li, Jiaqian Park, Kyung Soo Han, Kai Zhou, Xingwu Xu, Yao Nam, Jutaek Xu, Jin Shi, Xiaoyue Wei, Lei Lei, Yu Leo Moon, James J. Nat Nanotechnol Article Nutritional metal ions play critical roles in many important immune processes. Hence, effective modulation of metal ions may open up new forms of immunotherapy, termed as metalloimmunotherapy. Here, we demonstrate a prototype of cancer metalloimmunotherapy using cyclic dinucleotide (CDN) stimulator of interferon genes (STING) agonists and Mn(2+). We screened various metal ions and discovered specific metal ions augmented STING agonist activity, wherein Mn(2+) promoted a 12- to 77-fold potentiation effect across the prevalent human STING haplotypes. Notably, Mn(2+) coordinated with CDN STING agonists to self-assemble into a nanoparticle (CDN-Mn(2+) particle, CMP) that effectively delivered STING agonists to immune cells. CMP administered either by local intratumoral or systemic intravenous injection initiated robust anti-tumor immunity, achieving remarkable therapeutic efficacy with minute doses of STING agonists in multiple murine tumor models. Overall, CMP offers a new platform for local and systemic cancer treatments, and this work underscores the great potential of coordination nanomedicine for metalloimmunotherapy. 2021-09-30 2021-11 /pmc/articles/PMC8595610/ /pubmed/34594005 http://dx.doi.org/10.1038/s41565-021-00962-9 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: https://www.springernature.com/gp/open-research/policies/accepted-manuscript-terms
spellingShingle Article
Sun, Xiaoqi
Zhang, Yu
Li, Jiaqian
Park, Kyung Soo
Han, Kai
Zhou, Xingwu
Xu, Yao
Nam, Jutaek
Xu, Jin
Shi, Xiaoyue
Wei, Lei
Lei, Yu Leo
Moon, James J.
Amplifying STING Activation by Cyclic Dinucleotide-Manganese Particles for Local and Systemic Cancer Metalloimmunotherapy
title Amplifying STING Activation by Cyclic Dinucleotide-Manganese Particles for Local and Systemic Cancer Metalloimmunotherapy
title_full Amplifying STING Activation by Cyclic Dinucleotide-Manganese Particles for Local and Systemic Cancer Metalloimmunotherapy
title_fullStr Amplifying STING Activation by Cyclic Dinucleotide-Manganese Particles for Local and Systemic Cancer Metalloimmunotherapy
title_full_unstemmed Amplifying STING Activation by Cyclic Dinucleotide-Manganese Particles for Local and Systemic Cancer Metalloimmunotherapy
title_short Amplifying STING Activation by Cyclic Dinucleotide-Manganese Particles for Local and Systemic Cancer Metalloimmunotherapy
title_sort amplifying sting activation by cyclic dinucleotide-manganese particles for local and systemic cancer metalloimmunotherapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8595610/
https://www.ncbi.nlm.nih.gov/pubmed/34594005
http://dx.doi.org/10.1038/s41565-021-00962-9
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