摘要：SummaryAortic endothelial cell dysfunction is an early trigger of atherosclerosis, the major cause of the cardiovascular disease (CVD). Nanomedicines targeting vascular endothelium and lesions hold great promise as therapeutic solutions to vascular disorders. This study investigates the vascular delivery efficacy of polyurethane-polyurea nanocapsules (Puua-NCs) with pH-synchronized shell cationization and redox-triggered release. Fluorescent lipophilic dye DiI was encapsulated into Puua-NCs of variable sizes and concentrations.In vitrocellular uptake studies with human aortic endothelial cells showed that these Puua-NCs were taken up by cells in a dose-dependent manner. In apolipoprotein E-deficient mice fed a Western diet, a model of atherosclerosis, circulating Puua-NCs were stable and accumulated in aortic endothelium and lesions within 24 hours after intravenous administration. Treatment with thiol-reducing and oxidizing reagents disrupted the disulfide bonds on the surface of internalized NCs, triggering disassembly and intracellular cargo release. Ultimately, Puua-NCs are a potential redox-controllable cardiovascular drug delivery system.Graphical abstractDisplay OmittedHighlights•Aortic endothelial dysfunction precipitates atherosclerosis and cardiovascular disease•Nano-capsules show high affinity to aortic endothelium and atherosclerotic lesions•Offering a nanomedical approach to deliver drugs to improve cardiovascular outcomes•Disulfide bonds enable control of drug release by changing thiol redox statusNatural sciences; Biological sciences; Biological sciences research methodologies; Biological sciences tools
