Using doxorubicin and siRNA-loaded heptapeptide-conjugated nanoparticles to enhance chemosensitization in epidermal growth factor receptor high-expressed breast cancer cells.

The aim of this study was to develop the heptapeptide-conjugated active targeting nanoparticles for delivery of doxorubicin and siRNA to epidermal growth factor receptor (EGFR) high-expressed breast cancer cells. The active targeting nanoparticles were prepared by using a synthesized poly(D,L-lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) copolymer conjugated with a heptapeptide. The particle size of peptide-conjugated nanoparticles was less than 200 nm with narrow size distribution and the surface charge was negative. The uptake of peptide-conjugated nanoparticles was more efficient in EGFR high-expressed MDA-MB-468 cells than in EGFR low-expressed HepG2 cells by 3.9 folds due to peptide specific binding to EGF receptor followed by EGF receptor-mediated endocytosis. The nanoparticles were used to deliver doxorubicin and siRNA, and their in vitro release was faster in pH 4.0 (500 U lipase) than in pH 7.4. The IC50 of doxorubicin-loaded peptide-conjugated nanoparticles was lower than that of peptide-free nanoparticles by 2.3 folds in MDA-MB-468 cells. Similarly, the cellular growth inhibition of siRNA/DOTAP-loaded peptide-conjugated nanoparticles was 2.1 folds higher than that of peptide-free nanoparticles. In conclusion, the heptapeptide-conjugated PLGA-PEG nanoparticles provided active targeting potential to EGFR high-expressed MDA-MB-468 breast cancer cells, and a synergistic cytotoxicity effect was achieved by co-delivery of doxorubicin and siRNA/DOTAP-loaded peptide-conjugated nanoparticles.