ArticleBiomaterials research2026
Bioinspired TIMP-1 Nanoparticles Mimic Extracellular Vesicle Anti-angiogenic Activity in Ewing Sarcoma.
Article in Biomaterials research, 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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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Authors and funding
11 authors.
Funding
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Abstract
Anti-angiogenic therapies targeting the vascular endothelial growth factor (VEGF) axis have achieved transient benefits, as tumors rapidly activate compensatory vascular programs. Here, we present a bioinspired nanoplatform that reproduces the anti-angiogenic signaling of mesenchymal-stromal-cell-derived extracellular vesicles (EVs) by delivering the endogenous metalloproteinase inhibitor tissue inhibitor of metalloproteinases-1 (TIMP-1). Poly(methyl methacrylate) nanoparticles (NP_TIMP1) were engineered to retain TIMP-1 bioactivity, inhibit matrix metalloproteinase activity, and efficiently interact with endothelial cells. In vitro, NP_TIMP1 suppressed endothelial sprouting and tip-cell formation in 2-dimensional and 3-dimensional microfluidic systems. In zebrafish patient-derived xenografts of Ewing sarcoma, NP_TIMP1 localized to tumor-associated vessels and substantially reduced vascular infiltration, reproducing the efficacy of TIMP-1-enriched EVs. In contrast, soluble TIMP-1 failed to elicit these effects, indicating that nanoparticle-mediated delivery enhances protein stability and spatial engagement with the endothelium. This study establishes TIMP-1 as a key stromal regulator of angiogenesis and demonstrates that EV-mimetic nanoparticles can recapitulate its therapeutic potential, providing a scalable bioengineering approach to overcome the limitations of natural vesicles and develop next-generation anti-angiogenic nanotherapeutics.
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Registered trials
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