Blood Vessel Thromb Hemost. 2026 Sep 2;3(4):100210. doi: 10.1016/j.bvth.2026.100210. eCollection 2026 Nov.
ABSTRACT
Endothelial cells (ECs) line the vasculature and integrate hemodynamic, inflammatory, and metabolic cues that are crucial in maintaining vascular health. Endothelial dysfunction is a driver of thromboinflammatory conditions including atherosclerosis, thrombosis, stroke, and sepsis-induced multiorgan dysfunction syndrome. Therapies for these conditions that are given systemically fail to target the site of disease and can be associated with off-target side effects. EC-targeted nanoparticles represent a novel method of concentrating the drug- or gene-based therapy in ECs at the site of disease. Here, we describe studies of EC-directed nanoparticles in thromboinflammatory vascular diseases. We discuss challenges in the development of EC-targeted nanoparticle therapies, including issues with biosafety, delivery efficiency, scalability, and clinical translation. To target ECs, nanoparticle surfaces have been coated with ligand-directed antibodies or peptides against EC markers. EC targeting has also been achieved by coating nanoparticles with cell-mimicking membranes to leverage native homing pathways to sites of vascular injury. Stimuli-responsive nanoparticles have used EC or disease-specific cues to trigger drug release, for instance via reactive oxygen species or shear stress stimuli. EC-targeted nanoparticles extend the therapy circulation time, enhance drug accumulation at target sites, improve therapeutic efficacy, and reduce toxicity. In preclinical studies, EC-targeted nanoparticles have stabilized atherosclerotic plaques, degraded venous thrombi, and reduced cerebral infarct volume. Although EC-targeted nanoparticle therapies have not yet been approved for clinical use, advances in the design and safety of nanoparticles are narrowing the gap between experimental promise and clinical reality.
PMID:42893259 | PMC:PMC13676217 | DOI:10.1016/j.bvth.2026.100210