Enhanced delivery of Paclitaxel using electrostatically-conjugated Herceptin-bearing PEI/PLGA nanoparticles against HER-positive breast cancer cells.

We have developed a novel nanoparticle delivery system fabricated from polyethylenimine (PEI) and poly(d,l-lactide-co-glycolide) (PLGA), which were able to deliver the chemotherapeutic agent Paclitaxel, while the biomacromolecule Herceptin acted as a targeting ligand that was conjugated onto the surfaces of the nanoparticles via electrostatic interactions. In this study, these electrostatically-conjugated Herceptin-bearing PEI/PLGA nanoparticles (eHER-PPNs) were optimized and employed as vectors to target HER2-positive breast cancer cells. The eHER-PPNs had an average diameter of ∼ 280 nm and a neutral surface charge (1.00 ± 0.73 mV), which remained stable under physiological conditions. The anticancer effects of eHER-PPNs were investigated in HER2-positive BT474 cells and HER2-negative MCF7 cells. The eHER-PPNs showed enhanced cytotoxicity that was dependent on the receptor expression levels and the incubation time. These conjugated nanoparticles deliver Paclitaxel more efficiently (p<0.001) than unmodified PPNs, Herceptin and the combined effects of these two monotherapies. Furthermore, the chemically-conjugated Herceptin-bearing PEI/PLGA nanoparticles (cHER-PPNs) were fabricated as a comparison. The eHER-PPNs exhibited lower cell viability (46.7%) than that of cHER-PPNs (65.1%). The targeting ability of eHER-PPNs was demonstrated through confocal microscopy images and flow cytometry, which showed that eHER-PPNs displayed higher cellular uptake efficiency (p<0.001) in comparison with cHER-PPNs. Therefore, eHER-PPNs could provide promising platforms for the delivery of therapeutic drugs against HER2-positive breast cancers.