Platelet Membrane-Coated Nanoparticles Target Sclerotic Aortic Valves in ApoE−/− Mice by Multiple Binding Mechanisms Under Pathological Shear Stress

Hongbo Yang, 1,* Yanan Song, 1,* Jing Chen, 1,* Zhiqing Pang, 2 Ning Zhang, 1 Jiatian Cao, 1 Qiaozi Wang, 1 Qiyu Li, 1 Feng Zhang, 1 Yuxiang Dai, 1 Chenguang Li, 1 Zheyong Huang, 1 Juying Qian, 1 Junbo Ge 1 1Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, People’s Republic of China; 2School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, Shanghai 201203, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zheyong Huang; Juying QianDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, People’s Republic of ChinaTel +86-21-6404 1990 ext 2153Fax +86-21-6422 3006Email zheyonghuang@126.com; qian.juying@zs-hospital.sh.cnBackground: Aortic valve disease is the most common valvular heart disease leading to valve replacement. The efficacy of pharmacological therapy for aortic valve disease is limited by the high mechanical stress at the aortic valves impairing the binding rate. We aimed to identify nanoparticle coating with entire platelet membranes to fully mimic their inherent multiple adhesive mechanisms and target the sclerotic aortic valve of apolipoprotein E-deficient (ApoE−/−) mice based on their multiple sites binding capacity under high shear stress.Methods: Considering the potent interaction of platelet membrane glycoproteins with components present in sclerotic aortic valves, platelet membrane-coated nanoparticles (PNPs) were synthetized and the binding capacity under high shear stress was evaluated in vitro and in vivo.Results: PNPs demonstrated effectively adhering to von Willebrand factor, collagen and fibrin under shear stresses in vitro. In an aortic valve disease model established in ApoE−/− mice, PNPs exhibited good targeting to sclerotic aortic valves by mimicking platelet multiple adhesive mechanisms.Conclusion: PNPs could provide a promising platform for the molecular diagnosis and targeting treatment of aortic valve disease.Keywords: aortic valve, atherosclerosis, platelet membrane, nanoparticle, targeting