Objective To construct a platelet membrane bionic nanoprobe targeting PLT-RAP@NPs

and explore its immune escape

targeting and adhesion ability in vitro

as well as drug delivery after combination with UTMD. Methods RAP was loaded onto polymer PLGA by single emulsification-solvent evaporation technique

and a nanoprobe RAP@NPs was synthesized. Platelet membrane vesicles extracted by density-gradient centrifugation and repeated freeze-thaw cycles were used to prepare platelet membrane-coated biomimetic nanoprobe PLT-RAP@NPs by ultrasonic oscillation method. The particle size

potential and stability of nanoprobe were detected by dynamic light scattering technique. The microscopic morphology of the nanoprobe was observed by transmission electron microscopy. High-performance liquid chromatography was used to detect the encapsulation efficiency and drug loading efficiency of RAP in various proportions of nanoprobe to determine the best drug-loading protocol for RAP. DiI dye was encapsulated into PLGA to form DiI@PLGA and PLT-DiI@PLGA instead of the RAP@NPs and PLT-RAP@NPs for fluorescence detection

and then the NPs were co-incubated with RAW264.7 macrophages

foam cells

and endothelial cells in vitro. The phagocytosis and adhesion of these cells to the NPs were observed and analyzed by fluorescence microscope. For evaluating cell proliferation and cytotoxicity

CCK8 was used to evaluate the cell viability. In vitro dialysis and high-performance liquid chromatography were used to evaluate RAP release of PLT-RAP@NPs combined with UTMD. Results PLT-RAP@NPs were transparent and spherical

and showed a uniform size and clear core-shell structure. The surface of the core was coated with a film. The drug encapsulation efficiency reached the highest when 100 mg PLGA and 3 mg RAP entered the organic solvent; the encapsulation and drug loading efficiency were 60.35% and 2.18%

respectively. After RAW264.7 cells were co-incubated with DiI@PLGA and PLT-DiI@PLGA separately for 2 h

the orange-red fluorescence intensity of the DiI@PLGA group was significantly higher than that of the PLT-DiI@PLGA group

while the opposite result was obtained when the foam cells were co-incubated with the NPs. After TNF-α stimulated HUVEC up-regulated the expression of von Willebrand factor (vWF) and then co-incubated with the NPs for 2 h

a significant overlap between orange-red and green fluorescence in the PLT-DiI@PLGA group was shown

while no significant overlap was displayed in the DiI@PLGA group. With the increase of RAP concentration

the cell viability of the free RAP group gradually decreased

while the cell proliferation was less affected in PLT-RAP@NPs group. Slow release of RAP in RAP@NPs and PLT-RAP@NPs was shown

the release percentage was 42.12 % and 33.74 % at 72 h

and were raised to 75.57 % and 67.54 % after combination with UTMD

respectively. Conclusions The successfully prepared platelet membrane bionic nanoprobe PLT-RAP@NPs can inhibit macrophage phagocytosis

enhance foam cell uptake and improve endothelial cell adhesion through the biological function of platelet membrane

so as to achieve immune escape and targeting ability. Combined with UTMD

RAP controlled release of targeted can be realized.