Toxicity of Nanomaterials and Mechanisms of Endocytic Pathways

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Title: Toxicity of Nanomaterials and Mechanisms of Endocytic Pathways
Author: Zhang, Leshuai
Advisors: Andrew R. Barron, Committee Member
Xinrui Xia, Committee Member
Roger Narayan, Committee Member
Jim E. Riviere, Committee Member
Nancy A. Monteiro-Riviere, Committee Chair
Abstract: Engineered nanoparticles (NP) are small in size, large in surface area and can have different types of coating and functionalization. In addition, there are other characteristics of the NP such as unique chemical, mechanical, electrical, optical, and magnetic properties, as well as ability of tracking and quantification provide the possibility to utilize them in NP-based diagnosis or therapy. The potential for NP use in commercialized biomedical applications is increasing but the toxicity and biodistribution in biological systems is unknown. Since the 1990’s, a focus of NP research has been to uncover the associations between NP interactions in vitro and in vivo. However, NP interactions with skin has been limited. The goal of this research is to investigate the effects of several types of NP of different sizes, charges, and surface coatings on skin, or in human epidermal keratinocytes (HEK). Quantum dots (QD) have received attention due to their fluorescent properties. The penetration and interaction of QD in skin and the effect on HEK were studied. QD with different surface coatings remained in the stratum corneum layers or in the outer root sheath of hair follicles of rat skin and porcine skin. However, QD showed an increase in penetration in the dermis of the abraded skin but not tape-stripped rat skin. HEK viability decreased and cytokine release increased with QD. QD were internalized by HEK and localized freely or in cytoplasmic vacuoles. We investigated the interaction and uptake of carbon based NP such as multi-walled carbon nanotubes, amino acid derived single-walled carbon nanotubes, and fullerene functionalized peptides in HEK. The uptakes of NP were shown and the mechanism of how NP were incorporated into cells was also investigated. Carboxylic acid coated QD or fullerene peptides were utilized as targets to explore the endocytic mechanisms. These studies suggested that general pathways such as caveolae/lipid rafts, as well as specific receptors such as G protein coupled receptor and low density lipoprotein/scavenger receptors can regulate NP uptake in cells.
Date: 2009-12-08
Degree: PhD
Discipline: Comparative Biomedical Sciences

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