Authors
Yifeng Fang, Mengyan Tu, Xinru Tu, Hongbo Zhang, Yangyang Li, Junfen Xu
Published in
Biomaterials. Volume 335. Pages 124373. Jun 13, 2026. Epub Jun 13, 2026.
Abstract
Despite advances in oncology, the dual challenge of achieving precise tumor-targeted therapy while simultaneously activating antitumor immunity remains a major clinical barrier. In this study, we engineered a biocompatible copper-based platform, hyaluronic acid (HA) modified Cu ions based therapeutic (B-Cu/HA), that integrates selective tumor targeting, intrinsic cytotoxicity, and immune activation within a single therapeutic system. Leveraging the HA-CD44 interaction, B-Cu/HA exhibited preferential accumulation and prolonged retention in CD44-overexpressing tumors, while maintaining an excellent biosafety profile. Across multiple cancer models, B-Cu/HA robustly inhibited tumor progression. Mechanistically, it induced cuproptosis through upregulation of FDX1 and aggregation of lipoylated DLAT, and triggered ROS-mediated activation of the cGAS-STING pathway, promoting immunogenic cell death. Transcriptomic analysis revealed activation of hypoxia and cytokine signaling pathways, aligning with enhanced CD8+ T-cell cytotoxicity and remodeling of the tumor immune microenvironment. The animal models studies demonstrated that B-Cu/HA significantly suppressed tumor growth without systemic toxicity, and synergistically enhanced the efficacy of the immune checkpoint inhibitors anti-TIGIT. Together, these findings establish B-Cu/HA as a multifunctional, immunomodulatory formulation that offers a clinically translatable strategy to enhance tumor immunotherapy and overcome resistance in CD44-overexpressing tumors.
PMID:
42314235
Bibliographic data and abstract were imported from PubMed on 19 Jun 2026.
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