(250f) Gold Nanoconjugates: Targeted Drug Delivery, Biodistribution, and Toxicity

Authors: 
Liu, F., Wayne State University
Mao, G., Wayne State University

Gold nanoparticles (AuNPs) are particularly attractive due to their versatile surface chemistry, ease of imaging, and tunability to take advantage of the blood-brain barrier transport mechanisms. AuNPs have also been found to be among the most benign nanomaterials partially attributed to the inertness of bulk gold. Consequently, AuNPs are widely investigated for targeted delivery of drugs, genetic materials, antigens, and diagnostic agents. As a drug delivery carrier, the AuNP enables versatile conjugation chemistry with drugs and proteins. The size, shape, surface chemistry of the AuNP can be precisely tuned. Limited information about health and safety for nanomaterials makes it essential to identify potential harmful effects of exposure to AuNPs.  This poster sheds light on the effects of bovine serum albumin (BSA) coated AuNPs with various sizes on human embryonic stem cells (hESCs) and their subsequent neural precursor differentiations. After a 24-hour exposure only hESCs colonies treated with AuNPs of 1.5 nm in core diameter exhibited ongoing cell death. Furthermore, death of the hESC-derived neural precursor/progenitor cells was also observed when exposed to the 1.5 nm AuNPs. This poster also describes a tripartite nanoconjugate comprised of an AuNP drug carrier chemically conjugated to a transporter protein (wheat germ agglutinin coupled to horseradish peroxidase or WGA-HRP) and to the drug, theophylline. Our results show that a single administration of the nanoconjugate improved diaphragmatic activity at a dosage much lower than the effective systemic drug dose and restored majority of the respiratory drive. The effects lasted for 14 days. A biodistribution study using inductively coupled plasma mass spectrometry on the same animal model shows that the nanoconjugate was successful in targeting the respiratory neurons in the medulla. All the AuNPs and their nanoconjugates were characterized by UV-vis spectroscopy, transmission electron microscopy, dynamic light scattering, atomic force microscopy, and thermogravimetric analysis in order to determine the chemical composition and nanostructure on drug delivery, biodistribution, and toxicity.