Abstract
In several different atherosclerotic model mice, blocking CD47 with anti-CD47 antibody significantly reduced accumulation of arterial plaque. 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. 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. 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. 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.
Highlights
In a recent study, researchers from the Stanford University School of Medicine (USA) found that cells with surface antigen CD47 are extremely abundant in atherosclerotic plaque, and that CD47-blocking antibodies reverse defects in efferocytosis, normalize the clearance of diseased vascular tissue and ameliorate atherosclerosis in multiple mouse models
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 polyelectrolyte complex (PEC) were obtained in water or phosphate-buffered saline (PBS) and remained stable for 1 month
Summary
Researchers from the Stanford University School of Medicine (USA) found that cells with surface antigen CD47 are extremely abundant in atherosclerotic plaque, and that CD47-blocking antibodies reverse defects in efferocytosis, normalize the clearance of diseased vascular tissue and ameliorate atherosclerosis in multiple mouse models. In several different atherosclerotic mouse models, blocking CD47 with anti-CD47 antibody significantly reduced arterial plaque accumulation.[1]. How to use CD47 antibody to achieve effective drug delivery remains a key issue to be solved in future research. In the past few years, the preparation of polyelectrolyte complexes (PECs) through the electrostatic interaction of oppositely charged polyions, especially as a drug carrier or gene delivery system, has been widely studied by researchers.[2,3]. The preparation of PEC nanoparticles is relatively simple, and the synthesis requires minimal technical expertise and equipment. Without the need for toxic organic solvents and chemical cross-linking agents, PEC nanoparticles can be prepared under mild conditions and controlled. In several different atherosclerotic model mice, blocking CD47 with anti-CD47 antibody significantly reduced accumulation of arterial plaque
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