Surface modification of docetaxel nanocrystals with HER2 antibody to enhance cell growth inhibition in breast cancer cells.

Here, we describe docetaxel nanocrystals (DTX-NCs) surface-modified with Herceptin® (HCT) for combination cancer therapy. Using nano-precipitation and adsorption method, DTX-NCs and HCT-DTX-NCs were successfully prepared. The morphologies of DTX-NCs and HCT-DTX-NCs were characterized by field emission scanning electron microscopy (FE-SEM). The particle size and surface charge were evaluated by zeta-sizer and zeta-potential, respectively. Moreover, DTX-NCs and HCT-DTX-NCs were evaluated in terms of an in vitro drug release, cellular uptake and cytotoxicity. We hypothesized that because they contain water-soluble HCT, HCT-DTX-NCs would have increased particle size and in vitro drug release, and well maintained stability compared with DTX-NCs. We also hypothesized that HCT-DTX-NCs would exhibit higher uptake by, and toxicity toward, HER2-receptor-bearing cells. The DTX-NCs and HCT-DTX-NCs exhibited pebble-shaped morphologies with mean sizes of 472.8±138.1nm and 526.4±130.4nm, respectively. The zeta-potentials of DTX-NCs and HCT-DTX-NCs were -9.6±2.81mV and +10.4±2.87mV, respectively. The drug release profiles from HCT-DTX-NCs were more rapid than those from DTX-NCs and DTX. Both the DTX-NCs and HCT-DTX-NCs exhibited good stability in PBS (pH 7.4) at 4°C for 4 weeks. Moreover, HCT-DTX-NCs were associated with significantly greater uptake by, and cytotoxicity toward, MCF-7 cells, than DTX-NCs and DTX. In conclusion, HCT-adsorbed DTX-NCs exhibited good cellular uptake and cytotoxicity and may be useful anti-cancer treatments.