title: Formulation, characteristics and antiatherogenic bioactivities of CD36-targeted epigallocatechin gallate (EGCG)-loaded nanoparticles.
abstract: Intimal macrophages are determinant cells for atherosclerotic lesion formation by releasing inflammatory factors and taking up oxidized low-density lipoprotein (oxLDL) via scavenger receptors, primarily the CD36 receptor. (-)-Epigallocatechin-3-gallate (EGCG) has a potential to decrease cholesterol accumulation and inflammatory responses in macrophages. We made EGCG-loaded nanoparticles (Enano) using phosphatidylcholine, kolliphor HS15, alpha-tocopherol acetate and EGCG. 1-(Palmitoyl)-2-(5-keto-6-octene-dioyl) phosphatidylcholine (KOdiA-PC), a CD36-targeted ligand found on oxLDL, was incorporated on the surface of Enano to make ligand-Enano (L-Enano). The objectives of this study are to deliver EGCG to macrophages via CD36-targeted L-Enano and to determine its antiatherogenic bioactivities. The optimized nanoparticles obtained in our study were spherical and around 108 nm in diameter, and had about 10% of EGCG loading capacity and 96% of EGCG encapsulation efficiency. Compared to Enano, CD36-targeted L-Enano had significantly higher binding affinity to and uptake by macrophages at the same pattern as oxLDL. CD36-targeted L-Enano dramatically improved EGCG stability, increased macrophage EGCG content, delivered EGCG to macrophage cytosol and avoided lysosomes. L-Enano significantly decreased macrophage mRNA levels and protein secretion of monocyte chemoattractant protein 1, but did not significantly change macrophage cholesterol content. The innovative CD36-targeted nanoparticles may facilitate targeted delivery of diagnostic, preventive and therapeutic compounds to intimal macrophages for the diagnosis, prevention and treatment of atherosclerosis with enhanced efficacy and decreased side effects.
authors.affiliation: Department of Nutritional Sciences, Texas Tech University, Lubbock, TX 79409, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Nutritional Sciences, Texas Tech University, Lubbock, TX 79409, USA.
authors.forename: Shufang
authors.initials: S
authors.lastname: Nie
authors.affiliation: Department of Cell Physiology and Molecular Biophysics, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
authors.forename: Raul
authors.initials: R
authors.lastname: Martinez-Zaguilan
authors.affiliation: Department of Cell Physiology and Molecular Biophysics, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
authors.forename: Souad R
authors.initials: SR
authors.lastname: Sennoune
authors.affiliation: Department of Nutritional Sciences, Texas Tech University, Lubbock, TX 79409, USA. Electronic address: shu.wang@ttu.edu.
authors.forename: Shu
authors.initials: S
authors.lastname: Wang
mesh_terms: D050197:Atherosclerosis / Q000517:prevention & control*; D018955:CD36 Antigens / Q000737:chemistry*; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D053758:Nanoparticles
chemical_list: D018955:CD36 Antigens; D002392:Catechin; C045651:epigallocatechin gallate
keywords: (−)-Epigallocatechin-3-gallate; Atherosclerosis; Biocompatible and biodegradable; Macrophages; Nanoparticles; Phytochemicals; Targeted delivery