The Tango of cGAS-STING and Phagocytosis in Disease: From Molecular Mechanisms to Pharmacological Targeting.
5 affiliations
- 1Department of Geriatrics, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine, Beijing, 100049, People's Republic of China.
- 2GENERTEC Key Laboratory of Aerospace Medical Research and Transformation, Aerospace Medical Center, Aerospace Center Hospital, Beijing, 100049, People's Republic of China.
- 3Department of Blood Transfusion, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050000, People's Republic of China.
- 4Department of Neurology, Hohhot First Hospital, Fifth Clinical Medical College, Inner Mongolia Medical University, Hohhot, 010030, People's Republic of China.
- 5Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
Abstract
The cGAS-STING pathway is a central cytosolic DNA sensor that orchestrates innate immune responses beyond type I interferons, including autophagy, senescence, metabolism, and cell death. Phagocytosis-essential for clearing pathogens, debris, and apoptotic bodies-critically bridges innate and adaptive immunity. This review examines the bidirectional, context-dependent interplay between these fundamental processes and highlights how nanotechnology is uniquely positioned to exploit this crosstalk for therapeutic gain. We delineate four paradigms: STING activation upstream induces phagocytosis in lung inflammation, sepsis, spinal cord injury, cancer, and viral infection; phagocytosis initiates STING by delivering immunogenic cargo; positive feedback loops amplify antitumor immunity; and STING can suppress phagocytosis in obesity-driven adipose inflammation. Importantly, this axis exerts opposing regulatory effects across disease settings, being protective or pathogenic, synergistic or antagonistic, depending on cell type, stimulus, and pathological context. We further synthesize advanced nanoplatforms-biomimetic nanoparticles, hybrid membrane vesicles, DNA nanodevices, lymph node-targeted nanovaccines, and "Trojan horse" nanocapsules-engineered to co-deliver STING agonists, phagocytosis checkpoint inhibitors, and immunogenic cargo. These nanotherapies enhance antitumor and antimicrobial defense, resolve inflammation, and overcome barriers such as the blood-brain barrier. By integrating mechanism with nanobiotechnology, this review provides a conceptual framework for the cGAS -STING-phagocytosis network and a roadmap for next-generation nanomedicines treating cancer, infection, neurodegeneration, and inflammatory disorders.
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BibTeX
@article{wang2026tango,
title = {{The Tango of cGAS-STING and Phagocytosis in Disease: From Molecular Mechanisms to Pharmacological Targeting.}},
author = {Hongquan Wang and Jinxia Chen and Zhiji Wang and Fan Wu},
journal = {Drug design, development and therapy},
year = {2026},
month = oct,
doi = {10.2147/dddt.s650641},
url = {https://europepmc.org/article/MED/42953815},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - The Tango of cGAS-STING and Phagocytosis in Disease: From Molecular Mechanisms to Pharmacological Targeting.
AU - Hongquan Wang
AU - Jinxia Chen
AU - Zhiji Wang
AU - Fan Wu
PY - 2026
DA - 2026/10/24
JO - Drug design, development and therapy
DO - 10.2147/dddt.s650641
UR - https://europepmc.org/article/MED/42953815
AB - The cGAS-STING pathway is a central cytosolic DNA sensor that orchestrates innate immune responses beyond type I interferons, including autophagy, senescence, metabolism, and cell death. Phagocytosis-essential for clearing pathogens, debris, and apoptotic bodies-critically bridges innate and adaptive immunity. This review examines the bidirectional, context-dependent interplay between these fundamental processes and highlights how nanotechnology is uniquely positioned to exploit this crosstalk for therapeutic gain. We delineate four paradigms: STING activation upstream induces phagocytosis in lung inflammation, sepsis, spinal cord injury, cancer, and viral infection; phagocytosis initiates STING by delivering immunogenic cargo; positive feedback loops amplify antitumor immunity; and STING can suppress phagocytosis in obesity-driven adipose inflammation. Importantly, this axis exerts opposing regulatory effects across disease settings, being protective or pathogenic, synergistic or antagonistic, depending on cell type, stimulus, and pathological context. We further synthesize advanced nanoplatforms-biomimetic nanoparticles, hybrid membrane vesicles, DNA nanodevices, lymph node-targeted nanovaccines, and "Trojan horse" nanocapsules-engineered to co-deliver STING agonists, phagocytosis checkpoint inhibitors, and immunogenic cargo. These nanotherapies enhance antitumor and antimicrobial defense, resolve inflammation, and overcome barriers such as the blood-brain barrier. By integrating mechanism with nanobiotechnology, this review provides a conceptual framework for the cGAS -STING-phagocytosis network and a roadmap for next-generation nanomedicines treating cancer, infection, neurodegeneration, and inflammatory disorders.
SN - 1177-8881
ER -