A Nitric Oxide–Based STING Agonist Nanoadjuvant With ICD‐Derived Membrane Antigens Unleashes Robust Antitumor Immunity
4 affiliations
- 1Peking University Third Hospital
- 2Capital Medical University
- 3The First Affiliated Hospital of China Medical University
- 4Agency For Science, Technology and Research
Abstract
Despite significant advances in nanovaccine development, their efficacy remains hindered by poor antigen presentation, limited antigen repertoire, and suboptimal T cell priming. Immune adjuvants such as polyinosinic‐polycytidylic acid (POLY(I:C)) exert antitumor effects by promoting dendritic cell (DC) maturation and stimulating innate immunity, but their efficacy is limited by poor antigen presenting cell (APC) uptake and weak CD8+ T cell responses. Here, we propose a novel adjuvant strategy using nitric oxide (NO), a bioactive gaseous molecule, to upregulate MHC‐I and enhance DC cross‐presentation, thereby synergistically improving the adjuvant efficacy of POLY(I:C). We developed a nanovaccine, Im@NOnanoPL, by co‐encapsulating a preassembled complex of DOTAP, NOC‐18, and POLY(I:C) into a PLGA shell, which was further modified with DSPE‐PEG2000 and camouflaged with immunogenic cell death (ICD)–derived tumor membranes for broad‐spectrum tumor antigen coverage. Im@NOnanoPL elicited robust and durable CD8+ T cell responses, conferring near‐complete prophylactic protection and, in combination with αPD‐1 therapy, eradicating established tumors while inducing long‐term immune memory. Im@NOnanoPL constitutes a novel vaccine platform that integrates a gas‐based adjuvant with broad‐spectrum antigens, exhibiting strong translational potential.
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BibTeX
@article{xu2026nitric,
title = {{A Nitric Oxide–Based STING Agonist Nanoadjuvant With ICD‐Derived Membrane Antigens Unleashes Robust Antitumor Immunity}},
author = {Shuyu Xu and Yang Song and Tianjiao Zhang and Yan Wang and Mengxin Wang and Xinxin Xie and Qingfeng Chen and Xiaolong Liang},
journal = {Exploration (Beijing, China)},
year = {2026},
month = oct,
doi = {10.1002/exp2.70238},
url = {https://europepmc.org/article/PMC/PMC13654190},
note = {CC BY},
}
RIS
TY - JOUR
TI - A Nitric Oxide–Based STING Agonist Nanoadjuvant With ICD‐Derived Membrane Antigens Unleashes Robust Antitumor Immunity
AU - Shuyu Xu
AU - Yang Song
AU - Tianjiao Zhang
AU - Yan Wang
AU - Mengxin Wang
AU - Xinxin Xie
AU - Qingfeng Chen
AU - Xiaolong Liang
PY - 2026
DA - 2026/10/11
JO - Exploration (Beijing, China)
DO - 10.1002/exp2.70238
UR - https://europepmc.org/article/PMC/PMC13654190
AB - Despite significant advances in nanovaccine development, their efficacy remains hindered by poor antigen presentation, limited antigen repertoire, and suboptimal T cell priming. Immune adjuvants such as polyinosinic‐polycytidylic acid (POLY(I:C)) exert antitumor effects by promoting dendritic cell (DC) maturation and stimulating innate immunity, but their efficacy is limited by poor antigen presenting cell (APC) uptake and weak CD8+ T cell responses. Here, we propose a novel adjuvant strategy using nitric oxide (NO), a bioactive gaseous molecule, to upregulate MHC‐I and enhance DC cross‐presentation, thereby synergistically improving the adjuvant efficacy of POLY(I:C). We developed a nanovaccine, Im@NOnanoPL, by co‐encapsulating a preassembled complex of DOTAP, NOC‐18, and POLY(I:C) into a PLGA shell, which was further modified with DSPE‐PEG2000 and camouflaged with immunogenic cell death (ICD)–derived tumor membranes for broad‐spectrum tumor antigen coverage. Im@NOnanoPL elicited robust and durable CD8+ T cell responses, conferring near‐complete prophylactic protection and, in combination with αPD‐1 therapy, eradicating established tumors while inducing long‐term immune memory. Im@NOnanoPL constitutes a novel vaccine platform that integrates a gas‐based adjuvant with broad‐spectrum antigens, exhibiting strong translational potential.
SN - 2766-8509
SN - 2766-2098
ER -