title: Movement of a Quantum Dot Covered with Cytocompatible and pH-Responsible Phospholipid Polymer Chains under a Cellular Environment.
abstract: Quantum dots (QDs) were functionalized with well-defined polymer chains having both cytocompatibility and pH-responsiveness to monitor the movement of nanoparticles in a cellular environment with changing local pH. We used a triblock-type water-soluble polymer composed of three segments: (1) a pH-responsive poly[2-(N,N-diethylamino)ethyl methacrylate; DEAEMA] segment, (2) a poly[ω-(p-nitrophenyloxycarbonyl oligo(ethylene glycol)) methacrylate; MEONP] segment bearing an active ester group to react with an amino compound, and (3) a cytocompatible poly[(2-methacryloyloxyethyl phosphorylcholine; MPC) segment. Moreover, hydrophobic and carboxyl groups were attached as terminals of the polymer chain. The triblock-type polymer was attached to the QD surface through a hydrophobic layer, which was covered with the QD by hydrophobic interaction. This produced hybrid QD particles (QD/MPC polymer nanoparticles). The QD/MPC polymer nanoparticles had good water-dispersion ability after the modification. A fluorescence resonance energy transfer (FRET) phenomenon between QD and fluorescence dye (Alexa) was clearly observed at pH 7.4 and 9.0 when a fluorescence dye was reacted with the poly(MEONP) segment of the polymer. However, the efficiency decreased at pH 5.0. This was due to a change in the distance between the QD and the fluorescence dye in response to the protonation degree of the poly(DEAEMA) segment. The permeability of QD/MPC polymer nanoparticles through the cell membrane was enhanced by reacting the cell-penetrating peptide, octaarginine (R8), to the carboxyl group at the end of the polymer. The R8-QD/MPC polymer/Alexa nanoparticles attached onto the HeLa cell membrane surface within 15 min after they were added to the cell culture. This attachment initiated nanoparticle penetration of the cell membrane by endocytosis. The nanoparticles could be followed continuously as they moved in the cell culture. The change in the FRET index was determined during this process. Use of the R8-QD/MPC polymer/Alexa nanoparticle enabled us to determine nanoparticle location, based on the surrounding local pH. We concluded that QDs, modified with a cytocompatible and pH-responsible MPC polymer, provide a new imaging and transport tool in cell-based science and engineering.
authors: Department of Bioengineering and ‡Department of Materials Engineering, School of Engineering, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors: Yihua
authors: Y
authors: Liu
authors: Department of Bioengineering and ‡Department of Materials Engineering, School of Engineering, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors: Haruka
authors: H
authors: Oda
authors: Department of Bioengineering and ‡Department of Materials Engineering, School of Engineering, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors: Yuuki
authors: Y
authors: Inoue
authors: Department of Bioengineering and ‡Department of Materials Engineering, School of Engineering, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors: Kazuhiko
authors: K
authors: Ishihara
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage*; D031541:Fluorescence Resonance Energy Transfer; D005456:Fluorescent Dyes; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D045663:Quantum Dots; D014867:Water
chemical_list: D057846:Cell-Penetrating Peptides; D005456:Fluorescent Dyes; D010743:Phospholipids; D011108:Polymers; D014867:Water