ArticleInternational journal of nanomedicine2026
Enzyme/Reactive Oxygen Species-Dually Activated Hyaluronic Acid Nanocarriers Enable Celastrol Delivery for Site-Specific Therapy of Inflammatory Bowel Diseases and Colorectal Cancer.
Article in International journal of nanomedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: Conventional oral nanocarriers for intestinal diseases rely on single-responsive mechanisms and target a single pathological stage, failing to address the inflammation-carcinoma continuum. Celastrol (Cel)'s oral translation is limited by poor bioavailability and lack of lesion-specific targeting. To overcome these barriers, we constructed a hyaluronic acid (HA)-functionalized platform featuring dual enzyme/ROS-triggered release and CD44-mediated active targeting (HA@Cel/NPs) for treating ulcerative colitis (UC), colitis-associated colorectal cancer (CAC), and colon cancer. Methods: HA@Cel/NPs were fabricated using β-cyclodextrin and 4-(hydroxymethyl) phenylboronic acid as dual-responsive linkers. Physicochemical properties, drug release profiles, cellular uptake, anti-inflammatory activity, macrophage polarization, and anticancer activity were systematically evaluated in vitro. In vivo biodistribution and therapeutic efficacy were assessed in UC, CAC, and colon cancer mouse models, with anti-PD-L1 combination therapy in the colon cancer setting. Results: HA@Cel/NPs exhibited uniform size (76.87 ± 2.65 nm, PDI 0.166 ± 0.012), stayed stable for 14 days, and achieved ~71% Cel release under high H Conclusion: HA@Cel/NPs offer a versatile, dual-route platform that bridges inflammation management and cancer immunotherapy, distinguishing itself from single-mechanism or single-disease nanocarriers.
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