2. Academic Validation
  3. Engineering STING Nanoadjuvants for spatiotemporally-tailored innate immunity stimulation and cancer vaccination therapy

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

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. zaxu@chem.ecnu.edu.cn.
  • 8 State Key Laboratory of Chemical Biology & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. hjyu@simm.ac.cn.
  • 9 University of Chinese Academy of Sciences, Beijing, 100049, China. hjyu@simm.ac.cn.
  • 10 School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, China. hjyu@simm.ac.cn.
  • 11 Yantai Key Laboratory of Nanomedicine & Advanced Preparations, Yantai Institute of Materia Medica, Shandong, 264000, China. hjyu@simm.ac.cn.
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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