{"id":83801,"date":"2026-08-27T14:12:12","date_gmt":"2026-08-27T12:12:12","guid":{"rendered":"https:\/\/cri1149.fr\/?post_type=publication&p=83801"},"modified":"2026-08-27T14:12:13","modified_gmt":"2026-08-27T12:12:13","slug":"enhanced-glioblastoma-targeting-and-penetration-extracellular-matrix-remodeling-by-collagenase-functionalized-ferumoxytol-nanoparticles","status":"publish","type":"publication","link":"https:\/\/cri1149.fr\/en\/publication\/enhanced-glioblastoma-targeting-and-penetration-extracellular-matrix-remodeling-by-collagenase-functionalized-ferumoxytol-nanoparticles\/","title":{"rendered":"Enhanced Glioblastoma Targeting and Penetration: Extracellular Matrix Remodeling by Collagenase-Functionalized Ferumoxytol Nanoparticles"},"content":{"rendered":"\n

Abstract<\/h2>\n\n\n\n

Glioblastoma (GBM) contains a dense collagen-IV-rich extracellular matrix (ECM) that restricts intratumoral transport of therapeutic agents. To overcome this barrier, we engineered protease-responsive, collagenase-functionalized theranostic nanoparticles (TNP-collagenase) by conjugating collagenase-IV to the FDA-approved iron oxide nanoparticle ferumoxytol through a cathepsin B-cleavable linker, enabling tumor-specific enzyme activation. TNP-collagenase retained high MRI relaxivity and exhibited minimal cytotoxicity. In 3D tumor spheroids, TNP-collagenase significantly enhanced nanoparticle penetration compared with ferumoxytol alone. In an orthotopic U87MG mouse model, MRI demonstrated greater tumor accumulation of TNP-collagenase, reflected by significantly reduced tumor T2 relaxation times. TNP-collagenase combined with temozolomide (TMZ) induced significant tumor regression compared with PBS + TMZ and ferumoxytol + TMZ. Histological analyses confirmed degradation of perivascular collagen-IV and improved intratumoral distribution of therapeutics. These results establish enzyme-activated ECM remodeling as a nanomedicine strategy to enhance drug delivery and therapeutic efficacy in GBM while enabling noninvasive imaging of treatment response.<\/p>\n\n\n\n

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To overcome this barrier, we engineered protease-responsive, collagenase-functionalized theranostic nanoparticles (TNP-collagenase) by conjugating collagenase-IV to the FDA-approved iron oxide nanoparticle ferumoxytol through a cathepsin B-cleavable linker, enabling tumor-specific enzyme activation. 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