Date of Award

6-30-2016

Document Type

Open Access Thesis

Department

Chemistry and Biochemistry

First Advisor

Qian Wang

Abstract

Blood Brain Barrier (BBB) plays a main role as selective barrier which controls and limits access of chemicals, molecules and therapeutic agents from blood to brain. The BBB endothelial cells are connected by Tight Junctions (TJs) which close intracellular spaces between the endothelial cells and block the free diffusion of substances, therefore many potential drugs for treating human brain diseases cannot reach the brain in sufficient concentration. Recently, many studies have thrown an interest in development of nanoparticles for delivering drugs and imaging agents across BBB. Our research group has developed protein-polymer core-shell nanoparticles (PPCS-NPs) which demonstrate great potential for targeted delivery. In this work, Apolipoprotein E3 (ApoE3), which can be specifically bound to LDLR receptor on BBB endothelial cells, was chosen as a targeted motif. Nanoparticles conjugated with ApoE3 and fluorescently labelled ApoE3 (Fl-ApoE3) were successfully synthesized. The synthesis of ApoE3/ Fl-ApoE3 NPs with encapsulation of drugs and dyes is in progress. In vitro study of the uptake of ApoE3-NPs, Fl-ApoE3- NPs with and without encapsulation of drugs and dyes will be further investigated by using human umbilical vein endothelial cells (HUVECs) and brain microvascular endothelial cell line (hCMEC/D3) as BBB endothelial cell model.

Included in

Chemistry Commons

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