Date Approved

1-25-2023

Embargo Period

2-3-2024

Document Type

Thesis

Degree Name

M.S. Biomedical Engineering

Department

Biomedical Engineering

College

Henry M. Rowan College of Engineering

Advisor

Mark Byrne, Ph.D.

Committee Member 1

Vince Beachley, Ph.D.

Committee Member 2

Rachel Riley, Ph.D.

Committee Member 3

Jacek Wower, Ph.D.

Keywords

Chemotherapeutics, Controlled Release, Drug Delivery, Nanoparticles, Nucleic Acids

Subject(s)

Drug delivery devices

Disciplines

Biomedical Engineering and Bioengineering

Abstract

The next generation of anticancer agents will emerge from rationally designed nanostructured materials. This work involved the synthesis and characterization of novel hollow DNA-conjugated gold nanoparticles (DNA-AuNPs) for controlled drug delivery. Polyethyleneimine (PEI) was bound to citrate-capped AuNPs, forming polymer-shell nanoparticles. Dissolution of the gold core via iodine formed hollow core polymeric nanoparticles (HCPPs) and a high density of DNA (85 molecules/particle) containing daunorubicin was conjugated. Particles were spherical with an average diameter of 105.7±17.3 nm and zeta potential of 20.4±3.54 mV. We hypothesize the DNA backbone electrostatically condensed to the primary amines on the surface of the particle toroidally, weaving itself beneath. HCPPs released 225±44.6 mg more drug/cm3 than PEI capped AuNPs and showed release over 12 hours, an order of magnitude longer than PEI capped AuNPs. No change in release regarding DNA strand length or composition was noted. Increasing ionic concentration increased drug intercalation 64%, and intercalating drug to the DNA prior to nanoparticle conjugation resulted in 32% more drug loaded. A 10-fold decrease in the amine/phosphate ratio led to a 61% increase in drug intercalation. HCPPs did not aggregate in albumin and increased DNA stability and functionality when exposed to nuclease more than DNA conjugated gold nanoparticles. Drug delivery via HCPPs have promise to be more clinically efficacious compared to current nanoparticle designs.

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