Anticancer drug-inorganic nanohybrid and its cellular interaction.
An anticancer drug, methotrexate (MTX), has been successfully hybridized with layered double hydroxide (LDH) through co-precipitation route to produce MTX-LDH nanohybrids (MTX-LDH). According to the X-ray diffraction and FT-IR spectroscopy, it was confirmed that MTX molecules are stabilized in the interlayer space of LDHs by electrostatic interaction, maintaining their functional groups and structural integrity. According to the drug release study, the total amount of released MTX from the LDH lattice was determined to be larger under a simulated intracellular lysosomal condition (pH = 4.5) than simulated body fluid one (pH = 7.4). It is, therefore, expected that the MTX molecules in MTX-LDH can be effectively released in lysosomes, since the MTX release could be accelerated via ion-exchange reaction and dissolution of LDH in an acidic lysosomal condition. We also examined the anticancer efficacy of MTX-LDH in human breast adenocarcinoma MCF-7 cells. The cellular uptake of MTX was considerably higher in MTX-LDH-treated cells than in free MTX-treated cells, giving a lower IC50 value for the former than the latter. All the results demonstrated that the MTX-LDH nanohybrid allows the efficient drug delivery in cells, and thus enhances drug efficacy.
Kim
Ju Young
JY
Center for Intelligent Nano-Bio Materials (CINBM), Division of Nanoscience and Department of Chemistry, Ewha Womans University, Seoul 120-750, Korea.
Choi
Soo-Jin
SJ
Oh
Jae-Min
JM
Park
Taeun
T
Choy
Jin-Ho
JH
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry; D006801:Humans; D006878:Hydroxides / Q000737:chemistry; D007287:Inorganic Chemicals / Q000737:chemistry*; D008422:Materials Testing; D008727:Methotrexate / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size
D000970:Antineoplastic Agents; D004337:Drug Carriers; D006878:Hydroxides; D007287:Inorganic Chemicals; D008727:Methotrexate