title: Cellular uptake mechanism of an inorganic nanovehicle and its drug conjugates: Enhanced efficacy due to clathrin-mediated endocytosis.
abstract: We present the mechanism for the cellular uptake of layered double hydroxide (LDH) nanoparticles that are internalized into MNNG/HOS cells principally via clathrin-mediated endocytosis. The intracellular LDHs are highly colocalized with not only typical endocytic proteins, such as clathrin heavy chain, dynamin, and eps15, but also transferrin, a marker of the clathrin-mediated process, suggesting their specific internalization pathway. LDHs loaded with an anticancer drug (MTX-LDH) were also prepared to confirm the efficacy of LDHs as drug delivery systems. The cellular uptake of MTX was higher in MTX-LDH-treated cells than in MTX-treated cells, giving a lower IC50 value for MTX-LDH than for MTX only. The inhibition of the cell cycle was greater for MTX-LDH than for MTX only. This result clearly shows that the internalization of LDH nanoparticles via clathrin-mediated endocytosis may allow the efficient delivery of MTX-LDH in cells and thus enhance drug efficacy.
authors.affiliation: Center for Intelligent Nano-Bio Materials, Division of Nanoscience and Department of Chemistry, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: Jae-Min
authors.initials: JM
authors.lastname: Oh
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Choi
authors.forename: Sang-Tae
authors.initials: ST
authors.lastname: Kim
authors.forename: Jin-Ho
authors.initials: JH
authors.lastname: Choy
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D002966:Clathrin / Q000378:metabolism*; D004705:Endocytosis; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D008855:Microscopy, Electron, Scanning; D049329:Nanostructures / Q000648:ultrastructure; D014961:X-Ray Diffraction
chemical_list: D000970:Antineoplastic Agents; D002966:Clathrin