Comparison of adsorption and conjugation of Herceptin on poly(lactic-co-glycolic acid) nanoparticles - Effect on cell internalization in breast cancer cells

Surfaces of nanoparticles with are commonly modified to enhance the targeting effect. In this study, we performed surface modifications of docetaxel (DTX)-loaded poly(lactic-co-glycolic acid) nanoparticles (PNPs) with Herceptin (R) (HCT) to improve the internalization and cytotoxicity in breast cancer cells. The PNPs were prepared with surfactant, poly(ethylene-alt-maleic anhydride) (PEMA), including a number of carboxyl groups for conjugation. Three types of PNPs were prepared via different methods such as adsorption, charged adsorption, and bio-conjugation. The PNPs were evaluated in terms of physical properties, stability, cellular uptake and cytotoxicity. The docetaxel-loaded PNPs with HCT were successfully surface-modified with mean particle sizes of 338.4 +/- 59.8 nm (DTX-PNPs), 353.9 +/- 67.5 nm (HCT-A-DTX-PNPs), 544.8 +/- 301.7 nm (HCT-C-DTX-PNPs), and 499.1 +/- 71.9 nm (HCT-B-DTX-PNPs). Cellular uptake of HCT-B-PNPs was 5.0-, 4.4-, and 4.6-fold higher than that of PNPs in BT-474, SK-BR-3, and MCF-7 cells, respectively, at 2 h. At 40 mu g/mL, HCT-B-DTX-PNPs showed a higher cytotoxicity toward BT-474, SK-BR-3, and MCF-7 cells than the other formulations. In conclusion, HCT-B-DTX-PNPs were found to possess a higher affinity for breast cancer cells and induce a stronger cytotoxicity than that of other PNPs.