Tailored iron oxide nanoparticles for biomedical applications: Hydroxyethyl starch coating enhances endothelial biocompatibility.

Iron oxide nanoparticles (IONPs) offer promise for drug delivery and imaging, but their vascular safety requires thorough evaluation. Hydroxyethyl starch (HES) is a clinically used, biocompatible polysaccharide with potential as a nanoparticle coating to improve vascular safety. We synthesized novel hydroxyethyl starch-coated IONPs (IONPs@HES) and assessed their properties and effects on human microvascular endothelial cells (HMEC-1) under basal and inflammatory conditions. IONPs@HES showed magnetite cores, near-neutral charge, and reduced magnetic saturation, supporting biocompatibility. They were efficiently internalized without affecting viability or proliferation (20-500 μg/mL) and did not increase LPS-induced ICAM-1 expression. Autophagic activity, assessed by LC3 immunofluorescence and Cyto-ID flow cytometry, remained unchanged, suggesting preserved autophagic homeostasis. A modest increase in phosphorylated caveolin-1 (p-CAV1) was observed, with no enhancement under LPS stimulation. Co-treatment with indomethacin showed no additive toxicity. These findings support IONPs@HES as a biocompatible nanoplatform suitable for vascular-targeted cancer therapy, meriting further in vivo validation.