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Background 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.

Additional file 1: Figure S1. Stability of nanovesicles in PBS and PBS with 20% of fetal bovine serum (FBS). Nanovesicle sizes were measured using dynamic light scattering (n=3 per group). Results are presented as mean ± SD. Figure S2. The promotion of PLP-RvD1 treated macrophages to angiogenesis. (A) Capillary tube formation and (B) cell migration of HUVECs after cocultured with PBS, LP-RvD1 or PLP-RvD1 treated BMDMs. HUVECs cultured under normoxia were set as controls. Scalar bar, 100 μm and 200 μm, respectively. Figure S3. Circulation profiles of LP-RvD1 and PLP-RvD1 in healthy mice after intravenous injection (n=6 per group). Results are presented as mean ± SD.

Additional file 1: Figure S1. Size distribution and Transmission electron microscopy images. A Representative size distribution of LP and Neu-LPs. B Representative transmission electron microscopy images of LP and Neu-LP negatively stained with uranyl acetate. Scale bars, 50 nm. Figure S2. The stability of Neu-LP. Long-term stability of Neu-LP in water, monitored over 7 days (n = 3). Figure S3. The neutralization response and binding ability. A Neutralization dose response of proinflammatory factors (TNFα, IL1β, IL6, and CXCL2) by Neu LPs and LPs. *P < 0.05 and ***P < 0.001 compared with the 0mg/ml group. B the binding capacity of Neu LPs and LPs to inflammatory cytokines (TNFα, IL1β, IL6, and CXCL2). Figure S4. The evaluation of mouse MI/R model. Representative images of echocardiographic analysis of Sham mice or MI/R mice. Figure S5. Neu-LPs distribution in heart. Representative fluorescence imaging of Neu-LPs biodistribution in heart. Scale bars, 200 μm (yellow) and 50 μm (white). Figure S6. Macrophage recruitment in injured hearts. The quantitation of macrophage recruitment at day 3 post MI/R injury (n = 3). ***P < 0.001 compared with the PBS group. Figure S7. Heart histology at day 3. Representative A HE stain and B masson trichrome stain of the infarcted heart 3 days after treatment. Scale bars, 200 μm (red) and 1 mm (black). Figure S8. Cardiac function assessment. Left ventricular ejection fractions (LVEF) and fractional shortening (FS) were measured by echocardiography at different time points (baseline, 1 day, 10 days and 4 weeks) (n = 6 animals per group). *P < 0.05 and **P < 0.01 compared with the PBS group. Figure S9. The expression level of IgM. The expression level of IgM in the MI/R model mice following Neu-LPs injection (n = 3).