Premium
Cytosolic Delivery of Thiolated Mn‐cGAMP Nanovaccine to Enhance the Antitumor Immune Responses
Author(s) -
Chen Chengyun,
Tong Yuhong,
Zheng Youshi,
Shi Yingjun,
Chen Zhaowei,
Li Juan,
Liu Xiaolong,
Zhang Da,
Yang Huanghao
Publication year - 2021
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.202006970
Subject(s) - immune system , stimulator of interferon genes , cytosol , microbiology and biotechnology , immunotherapy , cancer immunotherapy , biology , chemistry , innate immune system , cancer research , immunology , biochemistry , enzyme
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 Mn 2+ coordinated cyclic dinucleotide nanovaccine (termed as Mn‐cGAMP NVs) to enable direct cytosolic co‐delivery of cGAMP and Mn 2+ to potentiate the antitumor immune response is presented. In the NVs, the fixation cGAMP with Mn 2+ 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.