title: Nanostructures Control the Hepatocellular Responses to a Cytotoxic Agent "Cisplatin".
abstract: In drug discovery programs, the alteration between in vivo and in vitro cellular responses to drug represents one of the main challenges. Since the variation in the native extracellular matrix (ECM) between in vivo and 2D in vitro conditions is one of the key reasons for such discrepancies, thus the utilization of substrate that likely mimics ECM characteristics (topography, stiffness, and chemical composition) is needed to overcome such problem. Here, we investigated the role of substrate nanotopography as one of the major determinants of hepatic cellular responses to a chemotherapeutic agent "cisplatin." We studied the substratum induced variations in cisplatin cytotoxicity; a higher cytotoxic response to cisplatin was observed for cells cultured on the nanopattern relative to a flat substrate. Moreover, the nanofeatures with grating shapes that mimic the topography of major ECM protein constituents (collagen) induced alterations in the cellular orientation and chromatin condensation compared to flat surfaces. Accordingly, the developments of biomimetic substrates with a particular topography could have potentials in drug development analyses to reflect more physiological mimicry conditions in vitro.
authors.affiliation: Cell-Materials Interaction Group, Biomaterials Unit, Nano-Life Field, International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.
authors.forename: Shimaa A
authors.initials: SA
authors.lastname: Abdellatef
authors.affiliation: Cell-Materials Interaction Group, Biomaterials Unit, Nano-Life Field, International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan ; Glycobiology Laboratory, Nagaoka University of Technology, 1603-1 Kamitomiokamachi, Nagaoka, Niigata 940-2137, Japan.
authors.forename: Riho
authors.initials: R
authors.lastname: Tange
authors.affiliation: Glycobiology Laboratory, Nagaoka University of Technology, 1603-1 Kamitomiokamachi, Nagaoka, Niigata 940-2137, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sato
authors.affiliation: MANA Foundry, International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Ohi
authors.affiliation: MANA Foundry, International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Nabatame
authors.affiliation: Cell-Materials Interaction Group, Biomaterials Unit, Nano-Life Field, International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan ; Graduate School of Advanced Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Taniguchi
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D006528:Carcinoma, Hepatocellular / Q000737:chemistry* / Q000188:drug therapy* / Q000503:physiopathology; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage* / Q000737:chemistry; D003603:Cytotoxins / Q000008:administration & dosage / Q000737:chemistry; D005109:Extracellular Matrix / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D008422:Materials Testing; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D049329:Nanostructures; D016896:Treatment Outcome; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; D003603:Cytotoxins; D002945:Cisplatin