Anticancer drug-layered hydroxide nanohybrids as potent cancer chemotherapy agents

Abstract

Methotrexate-layered double hydroxide (MTX-LDH) nanohybrid showed considerably enhanced cellular uptake and drug efficacy compared to free MTX. To evaluate the potential of drug-LDH nanohybrids as cancer chemotherapy agents, the present study was extended to encapsulate another anticancer drug, 5-fluorouracil (5-Fu) into LDH through coprecipitation method. The powder X-ray pattern of 5-Fu-LDH nanohybrid showed interlayer distance of 5.8 Å, which well corresponds to the longitudinal length of the drug molecule, indicating the successful intercalation. Drug efficacy of 5-Fu-LDH thus prepared was evaluated in several cancer cell lines such as human lung cancer, osteosarcoma, and hepatoma cells. Free 5-Fu, MTX, MTX-LDH, and doxorubicin (Dox) were also used for comparative studies. Our results demonstrated that both 5-Fu-LDH and MTX-LDH nanohybrids more effectively inhibited cancer cell proliferation than free 5-Fu and MTX, respectively, leading to cell death in a concentration-dependent manner. Among them, the highest drug efficacy was achieved by MTX-LDH nanohybrid, even higher than Dox, one of the most effective chemotherapy agents against a variety of cancers. Moreover, LDH itself did not exhibit acute cytotoxic effect up to 500 μg/ml as measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Therefore, this study suggests the great potential of anticancer drug-LDH nanohybrids as cancer chemotherapy agents. © 2007 Elsevier Ltd. All rights reserved.