多模态纳米粒靶向动脉粥样硬化易损斑块SR-A的体外研究

In vitro study of SR-A targeted multimodal nanoparticles for the detection of atherosclerotic vulnerable plaques

目的制备一种载硫酸葡聚糖(dextran sulfate,DS)的靶向清道夫受体A(scavenger receptor A,SR-A)的磁共振/光声双模态分子探针,研究其体外多模态成像及靶向性。材料与方法采用双乳化法和静电吸附法制备纳米粒[poly(lactic-co-glycolic acid),PLGA]-Fe3O4-DS,检测纳米粒的理化性质,研究其体外磁共振成像和光声成像情况,评估分子探针对活化巨噬细胞的靶向性。结果制备的PLGA-Fe3O4-DS纳米粒形状规则,大小均匀,分散性好,平均粒径为(263.93±21.38)nm,表面电位为(-20.63±2.61)mV,DS的连接率为90.06%。纳米粒对磁共振成像具有很好的负性增强作用,随着其浓度的增加,光声信号也逐渐增强。纳米粒与活化的巨噬细胞共孵育后,与非靶向组(PLGA-Fe3O4)相比,PLGA-Fe3O4-DS纳米粒大量聚集在细胞核周围。结论本研究制备的PLGA-Fe3O4-DS纳米粒具备良好的磁共振成像和光声成像能力,对SR-A有较高的亲和力,有望在分子水平分析受体在动脉粥样硬化斑块发展过程中的病理生理学机制。

Objective:To prepare a dualmodal molecular probe targeting scavenger receptor A(SR-A)loaded with dextran sulfate(DS),and to investigate its magnetic resonance(MR)/enhanced photoacoustic(PA)imaging and targeting ability in vitro.Materials and Methods:Nanoparticles[poly(lactic-co-glycolic acid),PLGA]-Fe3O4-DS were synthesized using double emulsification method and electrostatic adsorption method.The physicochemical properties and the MR/PA imaging capability were observed in vitro.The targeting efficiency of molecular probes for activated macrophages were evaluated.Results:The prepared PLGAFe3O4-DS nanoparticles have a regular shape,uniform size,and good dispersibility.The average particle diameter is 263.93±21.38 nm,the Zeta potential is-20.63±2.61 mV,and the DS connection rate is 90.06%.Nanoparticles have a good negative enhancement effect on magnetic resonance imaging.With the increase of its concentration,the photoacoustic signal gradually increases.Compared with the non-targeted group(PLGA-Fe3O4),the PLGA-Fe3O4-DS nanoparticles accumulated in large numbers around the nucleus after co-incubation of nanoparticles with activated macrophages.Conclusions:The PLGA-Fe3O4-DS nanoparticles were successfully prepared,which have good MR/PA imaging capabilities and high affinity for SR-A,providing the potential of analyzing the pathophysiological mechanism of receptors in the development of atherosclerotic plaques at the molecular level.