RGD peptide modified RBC membrane functionalized biomimetic nanoparticles for thrombolytic therapy

Abstract In recent years, the fabrication of nano-drug delivery systems for targeted treatment of thrombus has become a research hotspot. In this study, we intend to construct a biomimetic nanomedicine for targeted thrombus treatment. The poly lactic-co-glycolic acid (PLGA) was selected as the nanocarrier material. Then, urokinase and perfluoro-n-pentane (PFP) were co-loaded into PLGA by the double emulsification solvent evaporation method to prepare phase change nanoparticles PPUNPs. Subsequently, the RGD peptide-modified red blood cell membrane (RBCM) was coated on the surface of PPUNPs to prepare a biomimetic nano-drug carrier (RGD-RBCM@PPUNPs). The as-prepared RGD-RBCM@PPUNPs possessed a “core-shell” structure, have good dispersibility, and inherited the membrane protein composition of RBCs. Under ultrasound stimulation, the loaded urokinase could be rapidly released. In vitro cell experiments showed that RGD-RBCM@PPUNPs had good hemocompatibility and cytocompatibility. Due to the coated RGD-RBC membrane, RGD-RBCM@PPUNPs could effectively inhibit the uptake of macrophages. In addition, RGD-RBCM@PPUNPs showed better thrombolytic function in vitro. Overall, the results suggested that this biomimetic nanomedicine provided a promising therapeutic strategy for the targeted therapy of thrombosis. Graphical Abstract