Nanoengineered STING agonists for cancer therapy: toward immunodynamic control.
6 affiliations
- 1Department of Breast Surgical Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China.
- 2Department of Medical Oncology, Department of Experimental Therapeutics, Rare Cancer Center, National Cancer Center Hospital (NCCH), NCCH, National Cancer Center, Tsukiji 5-1-1, Chuo-ku, Tokyo, Japan.
- 3Department of Skin and Breast Tumor, University Clinical Hospital No. 4 Affiliated with the First Moscow State Medical University Named After I.M. Sechenov, Moscow, Russian Federation.
- 4Department of Breast Surgical Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China. [email protected].
- 5Department of Breast Surgical Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China. [email protected].
- 6Department of Breast Surgical Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China. [email protected].
Abstract
Activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is a mechanistically compelling strategy for cancer immunotherapy, but first-generation STING agonists have shown limited clinical activity despite clear pharmacodynamic induction of interferon-related signals. This translational gap suggests that therapeutic benefit depends not only on pathway engagement but also on where, in which cells, at what amplitude, and for how long STING is activated. In this review, we summarize the cellular context of cGAS-STING signaling, the pharmacological evolution and clinical experience of STING agonists, and the major barriers imposed by route, species differences, biological heterogeneity, and systemic inflammatory toxicity. We then examine how nanoengineering may improve agonist protection, cytosolic access, tissue and cell-type selectivity, and temporal exposure. Importantly, we distinguish improved delivery or tumor accumulation from direct evidence of altered signaling kinetics or a wider therapeutic window. Representative lipid, polymeric, inorganic, biogenic, biomimetic, antibody-directed, and prodrug-based platforms are evaluated together with mechanism-based combination sequencing, hematologic malignancy-specific considerations, biomarker-guided patient selection, repeated-dose safety, and manufacturability. Overall, nano-STING therapy should be developed toward immunodynamic control rather than simple delivery enhancement, with benefit judged by the relationship among delivery, cell-resolved pharmacodynamics, antitumor efficacy, and toxicity.
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BibTeX
@article{liu2026nanoengineered,
title = {{Nanoengineered STING agonists for cancer therapy: toward immunodynamic control.}},
author = {Naimeng Liu and Xiangyu Wang and Wenxiang Zhang and Yonemori Kan and Baranova Madina Petrovna and Zhongzhao Wang and Xiangyi Kong and Jing Wang},
journal = {Journal of hematology \& oncology},
year = {2026},
month = oct,
doi = {10.1186/s13045-026-01860-0},
url = {https://europepmc.org/article/MED/42902412},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Nanoengineered STING agonists for cancer therapy: toward immunodynamic control.
AU - Naimeng Liu
AU - Xiangyu Wang
AU - Wenxiang Zhang
AU - Yonemori Kan
AU - Baranova Madina Petrovna
AU - Zhongzhao Wang
AU - Xiangyi Kong
AU - Jing Wang
PY - 2026
DA - 2026/10/20
JO - Journal of hematology & oncology
DO - 10.1186/s13045-026-01860-0
UR - https://europepmc.org/article/MED/42902412
AB - Activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is a mechanistically compelling strategy for cancer immunotherapy, but first-generation STING agonists have shown limited clinical activity despite clear pharmacodynamic induction of interferon-related signals. This translational gap suggests that therapeutic benefit depends not only on pathway engagement but also on where, in which cells, at what amplitude, and for how long STING is activated. In this review, we summarize the cellular context of cGAS-STING signaling, the pharmacological evolution and clinical experience of STING agonists, and the major barriers imposed by route, species differences, biological heterogeneity, and systemic inflammatory toxicity. We then examine how nanoengineering may improve agonist protection, cytosolic access, tissue and cell-type selectivity, and temporal exposure. Importantly, we distinguish improved delivery or tumor accumulation from direct evidence of altered signaling kinetics or a wider therapeutic window. Representative lipid, polymeric, inorganic, biogenic, biomimetic, antibody-directed, and prodrug-based platforms are evaluated together with mechanism-based combination sequencing, hematologic malignancy-specific considerations, biomarker-guided patient selection, repeated-dose safety, and manufacturability. Overall, nano-STING therapy should be developed toward immunodynamic control rather than simple delivery enhancement, with benefit judged by the relationship among delivery, cell-resolved pharmacodynamics, antitumor efficacy, and toxicity.
SN - 1756-8722
ER -