Apolipoprotein E3 Mediated Targeted Brain Delivery of Reconstituted High Density Lipoprotein Bearing 3, 10, And 17 Nm Hydrophobic Core Gold Nanoparticles

We have developed a high density lipoprotein (HDL)-based platform for transport and delivery of hydrophobic gold nanoparticles (AuNP). The ability of apolipoprotein E3 (apoE3) to act as a ligand for the low-density lipoprotein receptor (LDLr) was exploited to gain entry of HDL with AuNP into glioblastoma cells. AuNP of 3, 10 and 17 nm diameter, the latter two synthesized by phase transfer process, were solubilized by integration into reconstituted HDL (rHDL). Absorption spectroscopy indicated the presence of stable particles with signature surface plasmon bands, while electron microscopy revealed AuNP embedded in rHDL core. The rHDL-AuNP complexes displayed robust binding to the LDLr, were internalized by the glioblastoma cells, and appeared as aggregated AuNP in the endosomal-lysosomal compartments. The rHDL-AuNP generated little cytotoxicity and were able to cross the blood brain barrier. The findings bear significance since they offer an effective means of delivering AuNP across tumor cell membrane