(547b) Uptake and Clearance of Spherical Gold Nanoparticles in 3D Liver Mimics

Technological advances in nanotechnology have led the design and synthesis of nanoparticles varying in size and shape that exhibit specific optical, electronic, and chemical properties. Among others, the pharmaceutical, cosmetic, and electronic industries are capitalizing on breakthroughs in nanoparticle technology. Biotechnology is one particular field realizing numerous advances as nanoparticles can be designed with characteristic dimensions resembling those of various biological molecules including bacteria, viruses, or even proteins and DNA. Current biotechnological applications of nanoparticles include imaging and sensing, as well as therapeutic applications in drug delivery and cancer therapy.

With the advent of the nanoparticle industry the prevalence of nanoparticles in everyday life and therefore the risk of human exposure whether it be intentional or inadvertent is increased. With the proven capability of nanoparticles to enter the blood stream after inhalation or ingestion, or directly through injection, evidence exists of nanoparticle accumulation in the liver. However, little is known about the specific uptake and clearance rates of nanoparticles by liver specific cells. In our studies we employ a novel 3D liver mimic culture system to investigate the uptake and clearance rates of 30 nm gold nanoparticles (AuNP).

The 3D liver mimic system is designed to duplicate the in vivo stratified hepatic structure where primary rat hepatocytes are separated from liver sinusoidal endothelial cells (LSECs) by the Space of Disse. In the 3D liver mimic, primary rat LSECs are layered above and separated from primary hepatocytes with the use of a porous self-assembled polyelectrolyte multilayered scaffold. This system enables cellular interactions through autocrine and paracine signaling pathways that are essential for the phenotypic maintenance of each cell type as well as hepatic-specific functions. Our research has shown AuNP uptake by hepatocytes to be directly proportional to both concentration and time during 24 hours of nanoparticle exposure. Results also indicate bare AuNPs are taken up by hepatocytes at a rate 7 times faster than AuNPs coated with a 5K MW PEG polymer. Current studies are underway to quantify the clearance rate of particles from hepatocytes over a 7 day culture period. Studies will also be conducted to understand the transfer and uptake kinetics of AuNPs by each cell type during culture in the 3D liver mimic. Computer tomography and fluorescence measurements are being used to image the sub-cellular localization of the gold nanoparticles. Together, these studies are expected to reveal insights into the interactions between liver tissues and nanoparticles.