Synthesis and characterization of atherosclerotic target anti-CD47 functionalized by nano-polyelectrolyte complexes between chitosan and hyaluronic acid and in vivo and in vitro targeting experiments

Background: In several different atherosclerotic model mice, blocking CD47 with anti-CD47 antibody significantly reduced accumulation of arterial plaque.

Objectives: We described the development of multifunctional positively charged polyelectrolyte complex (PEC) nanoparticles, designed to be stable at physiological salt concentrations and pH for effective targeted delivery in atherosclerosis.

Material and methods: These nanoparticles were obtained by charge neutralization using chitosan (CS) as the polycation and hyaluronic acid (HA) as the polyanion. An atherosclerotic-model antibody, the anti-CD47 antibody, was sorbed onto the particle surfaces in water and phosphate-buffered saline (PBS) for 4 h. The synthetic nanocarriers were exposed to vascular endothelial cells (VECs) in vitro to study their targeted adsorption to the cells, and the targeted distribution of nanocarriers was evaluated in vivo.

Results: We showed that the complexation process and the physicochemical properties of the resulting colloids were impacted by external parameters such as the charge mixing ratio and the polymer concentrations. Nonstoichiometric colloidal PECs were obtained in water or PBS (pH 7.4) and remained stable for 1 month. The morphology was studied with scanning electron microscopy (SEM). The average size of the CS-HA/CD47 nanoparticles was 375-620 nm, with a positive zeta potential. The CD47-targeted nanocarriers could be efficiently adsorbed to the surface of VECs in vitro, and their targeted distribution was evaluated in vivo.

Conclusions: Targeted nanocarriers can be effectively adsorbed to the surface of a VEC line and atheromatous plaque in vitro and in vivo. These results demonstrated that CS-HA/CD47 can be an effective carrier for targeted drug delivery in atherosclerosis.