Rationally Engineered Coronavirus-mimicking Protein Nanocage Platform for Glioblastoma Targeted Delivery and Immunity Regulation
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Le résumé fourni par la source
Abstract Glioblastoma (GBM) is one of the most aggressive and treatment-resistant brain tumors, owing to the dual challenges of the blood-brain barrier (BBB) and a profoundly immunosuppressive tumor microenvironment. However, few existing strategies are capable of simultaneously overcoming these two barriers, underscoring a critical scientific gap and the need for innovative therapeutic platforms that enable both effective BBB traversal and tumor immune reprogramming. Here, we present a coronavirus-mimicking protein nanocage platform (EcomPC) derived from Thermotoga maritima encapsulin, rationally engineered for the targeted and sustained delivery of interferon-α (IFN-α) to GBM lesions. Through strategic insertion of flexible linkers, cysteine-to-serine mutations, and modular surface functionalization via SpyTag/SpyCatcher chemistry, EcomPC enables intracellular self-assembly of IFN-α and glioma-specific targeting. In orthotopic GBM models, EcomPC–IFN demonstrates efficient BBB translocation, selective tumor accumulation, and potent anti-tumor efficacy. Mechanistically, localized IFN-α release induces tumor cell apoptosis and reprograms the immune microenvironment—characterized by increased CD8⁺ T cell infiltration, decreased Foxp3⁺ regulatory T cells, and a favorable chemokine shift. These therapeutic effects are not recapitulated by free IFN-α or untargeted nanocages, underscoring the essential role of both structural mimicry and ligand-guided delivery. Collectively, this work establishes EcomPC as a programmable, virus-inspired protein delivery platform capable of overcoming key physiological barriers in brain tumor immunotherapy, and lays the foundation for its broader application in CNS-targeted biologic delivery.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Rationally Engineered Coronavirus-mimicking Protein Nanocage Platform for Glioblastoma Targeted Delivery and Immunity Regulation
- Date Crossref
- 08/08/2025
- Éditeur
- openRxiv
- Type
- posted-content
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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Inner Mongolia University pays non établi dans la noticeUniversité ou école supérieure
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Inner Mongolia People's Hospital Department of Neurovascular Center pays non établi dans la noticeÉtablissement de santé
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Inner Mongolia Medical University Department of Neurosurgery pays non établi dans la noticeOrganisme public
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Inner Mongolia Medical College Hospital pays non établi dans la noticeÉtablissement de santé
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School of Life Sciences Inner Mongolia Key Laboratory for Molecular Regulation of the Cell pays non établi dans la noticeUniversité ou école supérieure
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The Affiliate Hospital of Inner Mongolia Meical University Department of Neurosurgery pays non établi dans la noticeUniversité ou école supérieure
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Department of Geriatric Medical Center pays non établi dans la noticeÉtablissement de santé
Inner Mongolia University, Department of Neurovascular Center — Inner Mongolia People's Hospital et Department of Neurosurgery — Inner Mongolia Medical University, avec 4 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.