ArticleNano letters2026
Enhanced Glioblastoma Targeting and Penetration: Extracellular Matrix Remodeling by Collagenase-Functionalized Ferumoxytol Nanoparticles.
Article in Nano letters, 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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6 authors.
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Abstract
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.
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