壳聚糖和透明质酸纳米聚电解质复合物吸附动脉粥样硬化特异抗体CD47的合成及体内外靶向实验

目的研究壳聚糖和透明质酸聚电解质复合物(PEC)纳米颗粒在生理盐水中的稳定浓度和物理化学参数对靶向抗体CD47有效吸附的影响以及合成的纳米载体对于血管内皮细胞的体外靶向性。方法壳聚糖(CS)作为聚阳离子与透明质酸(HA)(作为聚阴离子)发生电荷中和,合成壳聚糖和透明质酸聚电解质复合物纳米粒子。一模型抗体——动脉粥样硬化靶向抗体CD47在水或PBS溶液中,与纳米颗粒作用4 h后,定量吸附在CS-HA纳米颗粒表面。将合成的纳米载体体内外与血管内皮细胞及动脉粥样斑块相互作用,研究其靶向吸附作用。结果络合过程和胶体的物理化学性质受到外部因素的影响,如电荷混合比和聚合物浓度等参数。通过上述原理合成了非化学计量的CS-HA纳米胶体,在水或PBS(pH 7.4)溶液中保持稳定1个多月。扫描电镜检测其形貌特征。CS-HA/CD47抗体纳米颗粒平均粒径在375～620 nm之间,Zeta电位为正。CD47抗体靶向的纳米载体可在体外有效吸附到血管内皮细胞及动脉粥样斑块的表面。结论成功合成了CS-HA/CD47抗体纳米颗粒,该靶向纳米载体在体外可有效吸附到血管内皮细胞株及动脉粥样斑块的表面,是对动脉粥样硬化靶向给药具有应用前景的有效纳米载体。

Synthesis and characterization of atherosclerotic target antibody CD47 functionalized by nano-polyelectrolyte complexes between chitosan and hyaluronic acid

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.