Toxicity of Nanomaterials and Mechanisms of Endocytic Pathways
No Thumbnail Available
Files
Date
2009-12-08
Authors
Journal Title
Series/Report No.
Journal ISSN
Volume Title
Publisher
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.
Description
Keywords
endocytic pathways, toxicity, nanomaterial
Citation
Degree
PhD
Discipline
Comparative Biomedical Sciences