Pyridinium Rotor Strategy toward a Robust Photothermal Agent for STING Activation and Multimodal Image-Guided Immunotherapy for Triple-Negative Breast Cancer
The immunosuppressive tumor microenvironment in triple-negative breast cancer could hinder the response to thorough immunotherapy and diminish the antitumor efficacy. Although the STING pathway emerges as a promising target to remedy defects, uncertain drug delivery might lead to off-target inflammatory reactions. Here, we manifest a novel phototheranostic agent with an aggregation-induced emission property that guided the pharmacological activation of a STING agonist for photothermal immunotherapy to create an immunologically "hot" tumor. A pyridinium rotor strategy is proposed to develop a positively charged TBTP-Bz, which is stably coincorporated with a STING agonist MSA-2 into thermal-responsive exosome-liposome hybrid nanoparticles for tumor-targeting delivery. TBTP-Bz exhibits aggregation-enhanced NIR-II emission and a photoacoustic signal, accomplishing real-time tumor tracking. Its photothermal stimulation induces immunogenic cancer cell death and promotes the precise release of MSA-2, thus boosting STING activation and STING-mediated type I interferon production. Significantly, single-dose photoimmunotherapy effectively suppresses abscopal tumor growth and provokes an immune memory effect to inhibit postsurgical recurrent and rechallenged tumors. This demonstrates promising clinical potential for poorly immunogenic breast cancer.
Authors
- Xinwen Ou (ORCID: https://orcid.org/0000-0001-6694-7932)
- Xiuxin Lu
- Hanchen Shen (ORCID: https://orcid.org/0000-0002-3629-6873)
- Ping Shangguan
- Shipeng Ning (ORCID: https://orcid.org/0000-0003-3485-6598)
- Ben Zhong Tang (ORCID: https://orcid.org/0000-0002-0293-964X)
- Xiaoyuan Shawn Chen (ORCID: https://orcid.org/0000-0002-9622-0870)
- Kaiyuan Wang (ORCID: https://orcid.org/0000-0002-1114-6481)
- Tianfu Zhang (ORCID: https://orcid.org/0000-0001-6012-8856)
- Xinyan Zhu (ORCID: https://orcid.org/0009-0004-6981-9249)
- Xianqing Wei
- Meng Suo
Institutions
- Shenyang Pharmaceutical University (CN)
- Agency for Science, Technology and Research (SG)
- Shenzhen Institute of Information Technology (CN)
- Guangxi Medical University (CN)
- National University of Singapore (SG)
- Chinese University of Hong Kong (HK)
- Hong Kong University of Science and Technology (HK)
- Institute of Cancer Research (CA)
- Chinese University of Hong Kong, Shenzhen (CN)
- Université Bourgogne Franche-Comté (FR)
- Institute of Molecular and Cell Biology (SG)
- Guangzhou Medical University (CN)
Publication Details
- Journal
- Journal of the American Chemical Society
- Published
- 2025-02-20
- DOI
- https://doi.org/10.1021/jacs.4c15534
- Citations
- 57
- Primary Topic
- Nanoplatforms for cancer theranostics
- Type
- article
- Field-Weighted Citation Impact
- 38.43
Funders
- National Natural Science Foundation of China
- Research Grants Council, University Grants Committee
- Innovation and Technology Commission
- Hong Kong University of Science and Technology
- Science, Technology and Innovation Commission of Shenzhen Municipality
- Basic and Applied Basic Research Foundation of Guangdong Province