Engineering STING Nanoadjuvants for spatiotemporally-tailored innate immunity stimulation and cancer vaccination therapy

Fangmin Chen, Huijuan Zhang, Shiqin Li, Siyuan Ren, Lujia Huang, Zhixiong Cai, Lichen Yin, Mingyue Zheng, Xiaolong Liu, Zhiai Xu () and Haijun Yu ()
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Fangmin Chen: Chinese Academy of Sciences
Huijuan Zhang: Chinese Academy of Sciences
Shiqin Li: Chinese Academy of Sciences
Siyuan Ren: Chinese Academy of Sciences
Lujia Huang: Chinese Academy of Sciences
Zhixiong Cai: Mengchao Hepatobiliary Hospital of Fujian Medical University
Lichen Yin: Soochow University
Mingyue Zheng: Chinese Academy of Sciences
Xiaolong Liu: Mengchao Hepatobiliary Hospital of Fujian Medical University
Zhiai Xu: East China Normal University
Haijun Yu: Chinese Academy of Sciences

Nature Communications, 2025, vol. 16, issue 1, 1-21

Abstract: Abstract Spatiotemporally-tailored activation of dendritic cells (DC) in lymph nodes (LN) remains a critical challenge for effective cancer vaccination therapy. In this study, we show that photo/sonodynamic effect can trigger the nuclear transcription factor-kappa B (NF-κB) and stimulator of interferon genes (STING) pathways activation in DC. We engineers a library of spatiotemporally-tailored STING nanoadjuvants (SNA) by conjugating the photo/sonosensitizer and STING agonist onto the biodegradable polypeptide, and co-assembling with charge-modified polypeptides. The combination of antigen-loaded SNA vaccine (SNVac) with laser irradiation or ultrasound stimulation (namely SNVac-L or SNVac-US) efficiently facilitates DC activation and induces antigen-specific CD8+ T cell response in vivo comparing to the free mixture of antigen with STING agonist. We further demonstrate that SNVac-L monotherapy or combination therapy with immune checkpoint blockade (ICB) elicits antitumor immunity to reduce tumor size and prevent tumor relapse in multiple mouse tumor models. This study thus provides a potential translational strategy for spatiotemporally-tailored innate immunity stimulation of DC to potentiate cancer immunotherapy.

Date: 2025
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DOI: 10.1038/s41467-025-60927-7

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