EGFP-EGF1-conjugated poly(lactic-co-glycolic acid) nanoparticles, a new diagnostic tool and drug carrier for atherosclerosis
| Autor: | Gao-Hong Di, Hui Wang, Danying Liao, Wei Shi, Zhilin Wu, Jacques R. J. Davis, Bo Zhang, Liang Tang, Chen Chen |
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| Rok vydání: | 2019 |
| Předmět: |
Vascular smooth muscle
Biophysics Pharmaceutical Science Bioengineering 02 engineering and technology 010402 general chemistry 01 natural sciences Flow cytometry Biomaterials Tissue factor chemistry.chemical_compound In vivo Drug Discovery Fluorescence microscope medicine medicine.diagnostic_test Chemistry Organic Chemistry General Medicine 021001 nanoscience & nanotechnology In vitro 0104 chemical sciences PLGA 0210 nano-technology Drug carrier |
| Zdroj: | International Journal of Nanomedicine. 14:2609-2618 |
| ISSN: | 1178-2013 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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