Defense Date

2011

Document Type

Thesis

Degree Name

Master of Science

Department

Pharmacology & Toxicology

First Advisor

Shawn Holt

Abstract

Nanotechnology has recently emerged as a strong contributor toward research efforts to develop targeted systems of drug delivery in cancer therapy. Our work investigates the therapeutic potential of Targeted Charge-Reversal Nanoparticles (TCRNs), a novel nanoparticle with in vitro evidence of nuclear drug delivery. Using M12 prostate cancer cells, MDA-MB-231 breast cancer cells, and modified derivatives of these cell lines, we investigated the ability of Folic Acid-tagged TCRNs to deliver Nile Red and Dimethyl Indole Redfluorescent (DiR) fluorescent dyes to the nucleus of cells using confocal microscopy and in vivo biphontonic imaging using Xenogen® Technology. Confocal imaging with the SCP28 derivative of MDA-MB-231 cells shows nuclear association of the TCRNs over time, although specific nuclear deposition was unclear. Biophotonic imaging with M12 and SCP28 xenograft tumors in athymic nude mice shows retention of TCRNs in animals out to 7 days with minimal localization of TCRNs to tumor tissues. Our findings suggest that further characterization and manipulation of both the cells and the nanoparticle is necessary in order to make definitive claims regarding the TCRN’s ability to deliver fluorescent dyes, and eventually therapeutic compounds, to the nucleus of cells.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

December 2011

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