Aim To study the effect of stable concentration and physicochemical parameters of chitosan (CS) and hyaluronic acid (HA) polyelectrolyte complex (PEC) nanoparticles in physiological saline on the adsorption of targeting antibody CD47 and the target of synthesized nanocarriers in vitro and in vivo. Methods Chitosan was used as a polycation and hyaluronic acid as a polyanion to charge neutralize, and chitosan and hyaluronic acid polyelectrolyte complex nanoparticles were synthesized. A model antibody, atherosclerosis targeting antibody CD47, was adsorbed on the surface of CS-HA nanoparticles after 4 h of action with nanoparticles in water or PBS. The synthesized nanocarriers interact with vascular endothelial cells and atherosclerotic plaques in vitro and in vivo to study their targeting effects. Results The complexation process and the physicochemical properties of the colloid were affected by external factors such as charge mixing ratio and polymer concentration. Non-stoichiometric CS-HA nanocolloids were synthesized by the above principles and remained stable in water or PBS (pH 7.4) solution for more than one month. Scanning electron microscopy was used to detect the morphology. The average particle size of CS-HA/CD47 antibody nanoparticles was between 375 and 620 nm, and the zeta potential was positive. The nanocarriers targeted by the CD47 antibody can be efficiently adsorbed to the surface of vascular endothelial cell lines and atherosclerotic plaques. Conclusions CS-HA/CD47 antibody nanoparticles were successfully synthesized in this experiment. The targeted nanocarriers can effectively adsorb to the surface of vascular endothelial cells and atherosclerotic plaques in vitro and in vivo. It is an effective nanocarrier with application prospects for targeted administration of atherosclerosis.