TY - JOUR
T1 - Programmed initiation and enhancement of cGAS/STING pathway for tumour immunotherapy via tailor-designed ZnFe2O4-based nanosystem
AU - Yang, Jing
AU - He, Yuping
AU - Zhang, Meng
AU - Liang, Chenglin
AU - Li, Tongtong
AU - Ji, Tianjiao
AU - Zu, Mali
AU - Ma, Xu
AU - Zhang, Zhenzhong
AU - Liang, Chun
AU - Zhang, Qixu
AU - Chen, Youbai
AU - Hou, Lin
N1 - Publisher Copyright:
© 2023 The Authors. Exploration published by Henan University and John Wiley & Sons Australia, Ltd.
PY - 2023/12
Y1 - 2023/12
N2 - The cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)/stimulator of interferon genes (STING) signalling pathway has been a promising target for anticancer immunity, but rationally activating and enhancing this pathway in tumour cells is critical. Herein, a glutathione sensitive ZnFe2O4-based nanosystem is developed to programmatically initiate and enhance the STING signalling pathway in tumour cells. The prepared ZnFe2O4 nanoparticles were coated with cancer cell membrane (CCM), which enabled the nanosystem target tumour cells. In tumour cells, ZnFe2O4 nanoparticles could be disintegrated by responding to high level glutathione, and the released Fe3+ generated reactive oxygen species to induce the DNA leakage into the cytoplasm to stimulate cGAS. Then Zn2+ promoted cGAS-DNA phase separation to intensify the cGAS enzymatic activity. In addition, the low dose encapsulation of paclitaxel (PTX) acting as an antimitotic agent (ZnFe2O4-PTX@CCM) ensured the sustained activation of cGAS/STING pathway. The in vitro and in vivo results confirmed that ZnFe2O4-PTX@CCM elevated the cGAS/STING activity, promoted dendritic cell maturation, increased cytotoxic T lymphocyte and natural killer cells infiltration, eventually inhibiting the tumour progress and postoperative recurrence. This study provided feasible references on constructing STING activation nanosystem for tumour immunotherapy.
AB - The cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)/stimulator of interferon genes (STING) signalling pathway has been a promising target for anticancer immunity, but rationally activating and enhancing this pathway in tumour cells is critical. Herein, a glutathione sensitive ZnFe2O4-based nanosystem is developed to programmatically initiate and enhance the STING signalling pathway in tumour cells. The prepared ZnFe2O4 nanoparticles were coated with cancer cell membrane (CCM), which enabled the nanosystem target tumour cells. In tumour cells, ZnFe2O4 nanoparticles could be disintegrated by responding to high level glutathione, and the released Fe3+ generated reactive oxygen species to induce the DNA leakage into the cytoplasm to stimulate cGAS. Then Zn2+ promoted cGAS-DNA phase separation to intensify the cGAS enzymatic activity. In addition, the low dose encapsulation of paclitaxel (PTX) acting as an antimitotic agent (ZnFe2O4-PTX@CCM) ensured the sustained activation of cGAS/STING pathway. The in vitro and in vivo results confirmed that ZnFe2O4-PTX@CCM elevated the cGAS/STING activity, promoted dendritic cell maturation, increased cytotoxic T lymphocyte and natural killer cells infiltration, eventually inhibiting the tumour progress and postoperative recurrence. This study provided feasible references on constructing STING activation nanosystem for tumour immunotherapy.
KW - cGAS-STING pathway
KW - glutathione responsive
KW - tumour immunotherapy
KW - ZnFeO-based nanosystem
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U2 - 10.1002/EXP.20230061
DO - 10.1002/EXP.20230061
M3 - Article
C2 - 38264691
AN - SCOPUS:85180227410
SN - 2766-8509
VL - 3
JO - Exploration
JF - Exploration
IS - 6
M1 - 20230061
ER -