EGFP-EGF1-conjugated poly(lactic-co-glycolic acid) nanoparticles, a new diagnostic tool and drug carrier for atherosclerosis

Abstract

Background

EGFP-EGF1-conjugated poly(lactic-co-glycolic acid) (PLGA) nanoparticle (ENP) has a specific affinity to tissue factor (TF). The aim of this study was to investigate the target delivery of ENP to plaques and its uptake in a mouse model of atherosclerosis in vivo and in vitro.

Materials and methods

Coumarin-6- and 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbo cyanine iodide (DiR)-loaded ENPs were synthesized using a double-emulsion method. Mouse vascular smooth muscle cells (VSMCs) were induced with MCP-1 to obtain an increased TF expression. Fluorescence microscopy and flow cytometry assay were performed to examine the uptake of coumarin-6-loaded ENPs in cellular models. An animal model of atherosclerosis was established with an ApoE (−/−) mouse fed with continuous high-fat diets for 14 weeks. DiR-loaded ENPs (DiR-ENPs) were injected via the caudal vein. The distribution of DiR-ENPs was examined through organ imaging and confocal laser scanning microscopy.

Results

Results indicated TFs were highly expressed in the cellular model. The uptake of coumarin-6-loaded ENPs was significantly higher than that of common PLGA nanoparticles. Thickening of intima and lipid deposition in the aorta could be observed in atherosclerosis mouse models. Confocal laser scanning microscopy organ imaging showed ENPs accumulated in vessels with atherosclerotic plaques, which coincided with high expressions of TF.

Conclusion

This study showed that EGFP-EGF1-conjugated PLGA nanoparticles could be effectively delivered to atherosclerotic plaques in vivo and taken up by VSMCs with high TF expressions in vitro. Thus, it could be a promising carrier for targeted therapy of atherosclerosis.

Keywords:

• tissue factor
• atherosclerosis
• nanoparticle
• target delivery
• EGFP-EGF1

Acknowledgments

This work was supported by the National Natural Science Foundation of China (Nos 81500342 and 81600175). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author contributions

CC contributed to the conception and design of this study. ZW contributed to data acquisition. WS, BZ, and DL carried out animal experiments. GD and HW contributed to the analysis and interpretation of the data. JRJD and LT drafted the manuscript and critically revised it for important intellectual content. All authors contributed to data analysis, drafting and revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.