Redox-responsive polyurethane-polyurea nanoparticles targeting to aortic endothelium and atherosclerosis
Yuxiang Zhou,
David Hou,
Cristina Cusco Marigo,
Joaquín Bonelli,
Pau Rocas,
Fangzhou Cheng,
Xiaoqiu Yang,
Josep Rocas,
Naomi M. Hamberg,
Jingyan Han
Affiliations
Yuxiang Zhou
Vascular Biology Section, Evans Department of Medicine, Whitaker Cardiovascular Institute, Boston University School of Medicine, 650 Albany St. X 729, Boston, MA, USA
David Hou
Vascular Biology Section, Evans Department of Medicine, Whitaker Cardiovascular Institute, Boston University School of Medicine, 650 Albany St. X 729, Boston, MA, USA
Vascular Biology Section, Evans Department of Medicine, Whitaker Cardiovascular Institute, Boston University School of Medicine, 650 Albany St. X 729, Boston, MA, USA
Xiaoqiu Yang
Vascular Biology Section, Evans Department of Medicine, Whitaker Cardiovascular Institute, Boston University School of Medicine, 650 Albany St. X 729, Boston, MA, USA
Vascular Biology Section, Evans Department of Medicine, Whitaker Cardiovascular Institute, Boston University School of Medicine, 650 Albany St. X 729, Boston, MA, USA
Jingyan Han
Vascular Biology Section, Evans Department of Medicine, Whitaker Cardiovascular Institute, Boston University School of Medicine, 650 Albany St. X 729, Boston, MA, USA; Corresponding author
Summary: Aortic 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 vitro cellular 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.
