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

  • Nat Commun. 2025 Jul 1;16(1):5773. doi: 10.1038/s41467-025-60927-7.
Fangmin Chen  1  2 ,  Huijuan Zhang  1 ,  Shiqin Li  1 ,  Siyuan Ren  1  3 ,  Lujia Huang  1  2 ,  Zhixiong Cai  4 ,  Lichen Yin  5 ,  Mingyue Zheng  6 ,  Xiaolong Liu  4 ,  Zhiai Xu  7 ,  Haijun Yu  8  9  10  11
Affiliations
  • 1. State Key Laboratory of Chemical Biology & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • 2. University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 3. School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
  • 4. The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China.
  • 5. Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, 215123, China.
  • 6. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • 7. School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200241, China. [email protected].
  • 8. State Key Laboratory of Chemical Biology & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. [email protected].
  • 9. University of Chinese Academy of Sciences, Beijing, 100049, China. [email protected].
  • 10. School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, China. [email protected].
  • 11. Yantai Key Laboratory of Nanomedicine & Advanced Preparations, Yantai Institute of Materia Medica, Shandong, 264000, China. [email protected].
PMID: 40595553 DOI: 10.1038/s41467-025-60927-7
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.

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