M.S. Biomedical Engineering
Henry M. Rowan College of Engineering
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.
Chemotherapeutics, Controlled Release, Drug Delivery, Nanoparticles, Nucleic Acids
Drug delivery devices
Biomedical Engineering and Bioengineering
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.
Rucci, Brendan Guy, "POLYETHYLENEIMINE SHELL NUCLEIC ACID NANOSTRUCTURES FROM GOLD NANOPARTICLE TEMPLATE FOR CHEMOTHERAPEUTIC DRUG DELIVERY" (2023). Theses and Dissertations. 3082.
Available for download on Saturday, February 03, 2024