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

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.

EGFP-EGF1-conjugated poly (lactic-co-glycolic acid) nanoparticles as a carrier for the delivery of CCR2− shRNA to atherosclerotic macrophage in vitro

“…It has been proved that ENP's can mediate target delivery of TF-siRNA to injured brain micro-vascular endothelial cells (BMECs) for effective TF gene silencing in rats 19 . We also found that ENPs exhibited specific binding to atherosclerotic cellular model of vessel smooth muscle cells and plaques in an animal model 20 . We hypothesize that ENPs could also effectively adhere to atherosclerotic macrophages via binding to TF protein on cell surface.…”

“…CCR2-shRNA loaded PLGA nanoparticles, Coumarin-6 loaded EGFP-EGF1-PLGA nanoparticles and CCR2-shRNA loaded EGFP-EGF1-PLGA nanoparticles were prepared using a water in oil in water (w/o/w) double emulsion solvent evaporation method as previously described 22,23 . The characterization and loading efficiency of nanoparticles were determined as before 20 . Drug loading capacity (DLC) and drug encapsulation efficiency (DEE) were calculated according to the following equations:…”

Osteopontin-Targeted and PPARδ-Agonist-Loaded Nanoparticles Efficiently Reduce Atherosclerosis in Apolipoprotein E–/– Mice

“…The membranes were sealed with 5% (w/v) bovine serum albumin (BSA) at room temperature for 30 min. 18 , 31 , 50 The Sealed membranes were incubated with appropriate primary and secondary antibodies. The super-signal west picochemiluminescent substrate kit (Pierce Biotechnology; MA, USA) was used for blot development.…”

“…The samples were separated using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and transferred to nitrocellulose membranes. The membranes were sealed with 5% (w/v) bovine serum albumin (BSA) at room temperature for 30 min. ,, The Sealed membranes were incubated with appropriate primary and secondary antibodies. The super-signal west picochemiluminescent substrate kit (Pierce Biotechnology; MA, USA) was used for blot development.…”

A PEG-PLGA-based polymeric capsule as theranostic nanoplatform for active targeting atherosclerosis

“…There are generally no symptoms in the early stages of atherosclerosis and traditional detection techniques cannot easily, safely, and effectively detect the lesions in the early stages [8,9] . In recent years, there has been a rapid development in using nano-carrier technique as a tool for molecular imaging of atherosclerotic lesion [10][11][12] .…”