Apolipoprotein E3-mediated cellular uptake of reconstituted high-density lipoprotein bearing core 3, 10, or 17 nm hydrophobic gold nanoparticles

Abstract

Skylar T Chuang, Young-Seok Shon, Vasanthy Narayanaswami Department of Chemistry and Biochemistry, California State University Long Beach, Long Beach, CA, USA Abstract: We have developed a high-density lipoprotein (HDL)-based platform for transport and delivery of hydrophobic gold nanoparticles (AuNPs). The ability of apolipoprotein E3 (apoE3) to act as a high-affinity ligand for the low-density lipoprotein receptor (LDLr) was exploited to gain entry of HDL with AuNPs into glioblastoma cells. AuNPs of 3, 10, and 17 nm diameter, the latter two synthesized by phase transfer process, were solubilized by integration with phospholipids and apoE3, yielding reconstituted HDL (rHDL) bearing AuNPs. Ultraviolet–visible spectra of rHDL-AuNP indicated the presence of stable particles with surface plasmon band at ~530 nm. Transmission electron microscopy (TEM) of rHDL-AuNP revealed roughly spherical particles with AuNPs embedded in the core. The rHDL-AuNP particles displayed robust binding to the LDLr and were internalized by receptor-mediated endocytosis in glioblastoma cells. Confocal microscopy confirmed cellular uptake of AuNPs in the endosomal–lysosomal compartments, while TEM revealed intracellular aggregated AuNPs. Cell viability assay demonstrated that >85% of cells were viable with rHDL-AuNP treatment of 0.1–100 µg/mL for 24 hours. These findings are significant since they offer an effective means of delivering AuNPs across the cell membrane, which is particularly relevant in tumor cells that overexpress LDLr. Keywords: apolipoprotein E, gold nanoparticles, lipoproteins, HDL, cancer

Keywords

• Apolipoprotein E
• Gold nanoparticles
• Lipoproteins
• HDL
• Cancer