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author:

Chen, Chengyun (Chen, Chengyun.) [1] | Tong, Yuhong (Tong, Yuhong.) [2] | Zheng, Youshi (Zheng, Youshi.) [3] | Shi, Yingjun (Shi, Yingjun.) [4] | Chen, Zhaowei (Chen, Zhaowei.) [5] (Scholars:陈兆委) | Li, Juan (Li, Juan.) [6] (Scholars:李娟) | Liu, Xiaolong (Liu, Xiaolong.) [7] | Zhang, Da (Zhang, Da.) [8] | Yang, Huanghao (Yang, Huanghao.) [9] (Scholars:杨黄浩)

Indexed by:

EI SCIE

Abstract:

As a stimulator of interferon gene (STING), cyclic dinucleotide activates a broad cellular immune response for anti-cancer immunotherapy (CIT). However, the inherent of instability of 2 ' 3 '-cyclic-GMP-AMP (cGAMP) with poor cellular targeting, rapid clearance, and inefficient transport to the cytoplasm seriously hinders cGAMP potency. Here, a thiolated and Mn2+ coordinated cyclic dinucleotide nanovaccine (termed as Mn-cGAMP NVs) to enable direct cytosolic co-delivery of cGAMP and Mn2+ to potentiate the antitumor immune response is presented. In the NVs, the fixation cGAMP with Mn2+ ions not only improve its stability, but also potentiate the activation of STING. Meanwhile, the presence of polysulfides on the NVs surface allowed direct cytosolic delivery while avoiding degradation. In this way, the production of cytokines for activating T cells immunity is greatly elevated, which in turn suppressed the primary and distal tumors growth through long-term immune memory and led to long-term survival of poorly immunogenic B16F10 melanoma mice. Moreover, by further combining with anti-PD-L1 monoclonal antibody, synergistic T cells antitumor immune response is elicited. This work offers a promising strategy to enhance the potency of cGAMP, holding a considerable potential for CIT applications.

Keyword:

cancer immunotherapy cGAMP cytosolic delivery manganese STING pathway

Community:

  • [ 1 ] [Chen, Chengyun]Fuzhou Univ, MOE Key Lab Analyt Sci Food Safety & Biol, State Key Lab Photocatalysis Energy & Environm, Coll Chem, Fuzhou 350116, Peoples R China
  • [ 2 ] [Tong, Yuhong]Fuzhou Univ, MOE Key Lab Analyt Sci Food Safety & Biol, State Key Lab Photocatalysis Energy & Environm, Coll Chem, Fuzhou 350116, Peoples R China
  • [ 3 ] [Chen, Zhaowei]Fuzhou Univ, MOE Key Lab Analyt Sci Food Safety & Biol, State Key Lab Photocatalysis Energy & Environm, Coll Chem, Fuzhou 350116, Peoples R China
  • [ 4 ] [Li, Juan]Fuzhou Univ, MOE Key Lab Analyt Sci Food Safety & Biol, State Key Lab Photocatalysis Energy & Environm, Coll Chem, Fuzhou 350116, Peoples R China
  • [ 5 ] [Zhang, Da]Fuzhou Univ, MOE Key Lab Analyt Sci Food Safety & Biol, State Key Lab Photocatalysis Energy & Environm, Coll Chem, Fuzhou 350116, Peoples R China
  • [ 6 ] [Yang, Huanghao]Fuzhou Univ, MOE Key Lab Analyt Sci Food Safety & Biol, State Key Lab Photocatalysis Energy & Environm, Coll Chem, Fuzhou 350116, Peoples R China
  • [ 7 ] [Zheng, Youshi]Fujian Med Univ, United Innovat Mengchao Hepatobiliary Technol, Key Lab Fujian Prov, Mengchao Hepatobiliary Hosp, Fuzhou 350025, Peoples R China
  • [ 8 ] [Shi, Yingjun]Fujian Med Univ, United Innovat Mengchao Hepatobiliary Technol, Key Lab Fujian Prov, Mengchao Hepatobiliary Hosp, Fuzhou 350025, Peoples R China
  • [ 9 ] [Liu, Xiaolong]Fujian Med Univ, United Innovat Mengchao Hepatobiliary Technol, Key Lab Fujian Prov, Mengchao Hepatobiliary Hosp, Fuzhou 350025, Peoples R China
  • [ 10 ] [Zhang, Da]Fujian Med Univ, United Innovat Mengchao Hepatobiliary Technol, Key Lab Fujian Prov, Mengchao Hepatobiliary Hosp, Fuzhou 350025, Peoples R China

Reprint 's Address:

  • 张达 杨黄浩

    [Zhang, Da]Fuzhou Univ, MOE Key Lab Analyt Sci Food Safety & Biol, State Key Lab Photocatalysis Energy & Environm, Coll Chem, Fuzhou 350116, Peoples R China;;[Yang, Huanghao]Fuzhou Univ, MOE Key Lab Analyt Sci Food Safety & Biol, State Key Lab Photocatalysis Energy & Environm, Coll Chem, Fuzhou 350116, Peoples R China;;[Zhang, Da]Fujian Med Univ, United Innovat Mengchao Hepatobiliary Technol, Key Lab Fujian Prov, Mengchao Hepatobiliary Hosp, Fuzhou 350025, Peoples R China

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Source :

SMALL

ISSN: 1613-6810

Year: 2021

Issue: 17

Volume: 17

1 5 . 1 5 3

JCR@2021

1 3 . 0 0 0

JCR@2023

ESI Discipline: MATERIALS SCIENCE;

ESI HC Threshold:142

JCR Journal Grade:1

CAS Journal Grade:2

Cited Count:

WoS CC Cited Count: 64

SCOPUS Cited Count: 49

ESI Highly Cited Papers on the List: 0 Unfold All

WanFang Cited Count:

Chinese Cited Count:

30 Days PV: 0

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