The antiatherogenic effects of targeted epigallocatechin gallate ‐ loaded nanoparticles (1045.41)

Abstract

Objective: The objectives of this study were to incorporate scavenger receptor target ligands on the surface of biocompatible and biodegradable epigallocatechin gallate (EGCG)‐loaded nanoparticles (E‐LNP), to evaluate their target specificity to macrophages in vitro and atherosclerotic lesions in LDLr‐/‐ mice.Method: E‐LNP were synthesized using a sonication method. Particle size, zeta potential and morphology were determined using a transmission electron microscope and Brookhaven analyzer. The target specificity to macrophages (in vitro) and to atherosclerotic lesions in LDLr‐/‐ mice (in vivo) was measured using a fluorescence microscopy and an IVIS® Lumina XR imaging system, respectively. Macrophage cholesterol content and EGCG uptake were measured using a HPLC method. After intravenous injection of E‐LNP once per week for 20 weeks, the aortic lesion was quantified by a microscope and image J software.Results— E‐LNP are negatively charged and less than 100 nm in diameter. As compared to nanoparticles without target ligands, targeted E‐LNP significantly increased macrophage EGCG content and decreased macrophage expression of monocyte chemoattractant protein 1 (MCP‐1). The target ligands significantly increased the binding and uptake of those nanoparticles to THP‐1 derived macrophages and improved the target specificity to atherosclerotic lesions in LDLr‐/‐ mice.Conclusions— Targeted E‐LNP have a potential for decreasing aortic cholesterol accumulation and inflammatory responses through targeting to macrophages and foam cells in atherosclerotic lesions.Grant Funding Source: Supported by NIH 1R15AT007013‐01