{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE334nnn/GSE334430/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE334430"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Bioinspired TIMP-1 Nanoparticles Mimic Extracellular Vesicle Anti-angiogenic Activity in Ewing Sarcoma","description":"Anti-angiogenic therapies targeting the VEGF/VEGFR 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 TIMP-1. Poly(methyl methacrylate) nanoparticles (NP_TIMP1) were engineered to retain TIMP-1 bioactivity, inhibit matrix metalloproteinase (MMP) activity, and selectively target endothelial cells. In vitro, NP_TIMP1 suppressed endothelial sprouting and tip-cell formation in 2D and 3D microfluidic systems. In zebrafish patient-derived xenografts of Ewing sarcoma, NP_TIMP1 localized to tumor-associated vessels and significantly 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.","dates":{"publication":"2026/09/11"},"accession":"GSE334430","cross_references":{"GSM":["GSM9788610","GSM9788611","GSM9788609","GSM9788607","GSM9788608","GSM9788605","GSM9788606","GSM9788612","GSM9788613"],"GPL":["24676"],"GSE":["334430"],"taxon":["Homo sapiens"]}}