Hollow Polyethyleneimine Nanoparticles with Drug Loaded DNA for Chemotherapeutic Applications

The next generation of anticancer agents are emerging 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 AuNPs, forming polymer-shell nanoparticles. Dissolution of the gold core via iodine formed hollow core polymeric nanoparticles (HCPNPs) and a high density (85 molecules/particle) of DNA intercalated with 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 within the polymer shell. During the DNA intercalation process, increasing the ionic concentration and decreasing the amine/phosphate ratio 10-fold increased drug intercalation 64 % and 61 %, respectively, allowing us to determine the optimal method of particle synthesis. As intercalation sites increased with increasing DNA strand length, drug loading increased. An average of 874 +/- 40.1 daunorubicin molecules were loaded per HCPNP. HCPNPs with drug intercalated DNA have strong potential to be clinically efficacious drug delivery vehicles due to the versatility of DNA and high drug loading capacities. This work details the synthesis and characterization of a novel formulation of hollow polyethyleneimine nanoparticles developed from a gold nanoparticle template. The nanoparticles are further loaded with DNA which has intercalated a chemotherapeutic agent. The findings suggest that the platform would serve as a valuable tool for chemotherapeutic drug delivery. image