Ultrasound-Energized OX40L-Expressing Biohybrid for Multidimensional Mobilization of Sustained T Cell-Mediated Antitumor Immunity and Potent Sono-Immunotherapy
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Le résumé fourni par la source
Harnessing immunostimulation to reinvigorate antitumor effector immune cells represents a promising strategy for tumor eradication. However, achieving durable clinical outcomes necessitates multidimensional activation to sustain robust immune responses. Here, we present an ultrasound-empowered living biohybrid that strategically mobilizes T-cell-mediated immunity for potent tumor sono-immunotherapy. Through synthetic biology, we engineer bacteria to express a fusion protein encoding the costimulatory OX40 ligand (OX40L), and further functionalize them with a high-performance polymer sonosensitizer tethered via a reactive oxygen species-cleavable linker. Upon ultrasound irradiation, the sono-activated nanocargoes detach from the bacterial surface, facilitating cellular entry and exposing immune-stimulating OX40L. The potent sonodynamic effects, coupled with the native immunogenicity of bacteria, promotes tumor-associated antigen release, fosters a proinflammatory microenvironment, and drives dendritic cell maturation, thereby priming cytotoxic T-cell activation. The OX40L expressed by the engineered bacteria amplifies and sustains T-cell activity, orchestrating a robust and durable antitumor response. This cascade-amplified immune activation effectively suppresses tumor growth, induces long-lasting immune memory, and provides protection against tumor metastasis and recurrence, significantly enhancing survival outcomes. By integrating ultrasound-energized nanoadjuvants with costimulatory immune boosters, this hybrid living biotherapeutic platform offers a versatile and powerful strategy for multidimensional immune activation, advancing the frontier of cancer sono-immunotherapy.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Ultrasound-Energized OX40L-Expressing Biohybrid for Multidimensional Mobilization of Sustained T Cell-Mediated Antitumor Immunity and Potent Sono-Immunotherapy
- Date Crossref
- 09/04/2025
- Éditeur
- American Chemical Society (ACS)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Nankai University pays non établi dans la noticeUniversité ou école supérieure
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Chinese Academy of Medical Sciences & Peking Union Medical College pays non établi dans la noticeUniversité ou école supérieure
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Institute of Biomedical Engineering pays non établi dans la noticeStructure de recherche
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and College of Life Sciences State Key Laboratory of Medicinal Chemical Biology pays non établi dans la noticeUniversité ou école supérieure
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Chinese Academy of Medical Sciences and Peking Union Medical College Institute of Biomedical Engineering pays non établi dans la noticeUniversité ou école supérieure
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Tianjin Key Laboratory of Biomedical Materials and Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy pays non établi dans la noticeStructure de recherche
Nankai University, Chinese Academy of Medical Sciences & Peking Union Medical College et Institute of Biomedical Engineering, avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.