PhD Proposal: Luke Mortensen
Analysis of Quantum Dot Skin Penetration in a Barrier Compromised In Vivo Model
Nanoscale discovery and application is an important branch of modern science that has produced basic research and high-level device discovery. This has translated into an explosion in the amount of nanoparticles (NP) that are used in a wide variety of scientific disciplines and consumer products. In the biomedical and electronics fields, quantum dot semiconductor nanoparticles (QD) are valued for their optical and electrical properties. The most important of these is their fluorescence -- unique due to high quantum yield, broad excitability, and narrow emission bandwidth. This feature has made them of great interest in the life sciences as targeted probes to examine biological processes, cell features, and even potentially medical diagnostics and drug delivery. Along with biological and medical applications, QD are being implemented in LED displays, data storage, and information processing. Their growing presence in these applications means an increased risk of human exposure in manufacturing, research, and consumer use. However, very few studies have looked at the ability of QD to penetrate the skin- the most common exposure route- and the results of those that exist are conflicting. Additionally, no research has examined the effect of a damaged skin barrier; such as can occur with mild ultraviolet radiation (UVR) exposure. This is of crucial interest as recent findings have provided evidence of in vitro toxicity and long term retention in the body for most QD surface chemistries. Hence, this proposal focuses on defining the effect of UVR damage and QD characteristics on the penetration of NP through the skin barrier in an in vivo model. We hypothesize that the extent of QD skin penetration is determined by the surface chemistry of the QD and the barrier status of the skin. To prove our hypothesis, we will evaluate the skin barrier status and NP penetration depth, elucidate the driving mechanism, and develop a novel optical system to improve imaging capabilities.
The first aim of our proposal is to evaluate UVR induced barrier loss and recovery time using an established technique of transepidermal water loss (TEWL) in a murine SKH-1 in vivo model and correlate barrier loss to increased skin penetration of a characteristic QD using histology and TEM techniques. The second aim will demonstrate a difference in skin barrier penetration of positively and negatively charged hydrophilic QD using the induced UVR barrier defect and processing techniques developed in our first aim. Our final aim proposes to develop a whole tissue reflectance and fluorescence confocal microscopy system, which will be used to image tissue features and penetration of a single QD as deep as the reticular dermis to eliminate tissue processing artifacts and allow superior quantitative analysis. Our study will increase understanding of the mechanisms and driving forces of skin barrier function against nanoparticles and enable future work in more specific targeting of nanoparticles, to prevent or to enhance penetration. This knowledge could be used to develop powerful therapeutic agents and decreased penetration cosmetic nanoparticles.