title: Design and synthesis of temperature-responsive polymer/silica hybrid nanoparticles and application to thermally controlled cellular uptake.
abstract: This study reports the development of temperature-responsive polymer/silica hybrid nanoparticles and their application to temperature-dependent intracellular uptake of hydrophobic encapsulated fluorescence molecules. Amphiphilic diblock copolymer comprising a temperature-responsive segment, poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) [P(NIPAAm-co-DMAAm)] and a trimethyoxysilyl-containing hydrophobic segment was synthesized (PBM-b-ND); this amphiphilic diblock copolymer self-assembled in an aqueous solution, and temperature-responsive polymer/silica hybrid fluorescence nanoparticles were fabricated via a base-catalyzed sol-gel process. The fluorescence probe rhodamine DHPE or boron dipyrromethene derivative was encapsulated into the polymer core with a silica network in a stable manner. Other types of polymer/silica hybrid fluorescence nanoparticles were also developed using either homo-PNIPAAm (PBM-b-N) or homo-PDMAAm (PBM-b-D) segments, instead of P(NIPAAm-co-DMAAm). While PBM-b-D did not exhibit a temperature-dependent phase transition (hydrophilic characteristic), PBM-b-N and PBM-b-ND exhibited temperature-dependent phase transition (hydrophilic/hydrophobic) at 32°C and 38°C, respectively. The cellular uptake of PBM-b-N was clearly observed at both 37°C and 42°C, while the cellular uptake of PBM-b-D was minimal at these temperatures. On the other hand, significant enhancement in the intracellular uptake of PBM-b-ND was observed at 42°C, compared to its uptake at a lower temperature of 37°C. These results indicated that temperature-responsive polymer/silica hybrid nanoparticle, PBM-b-ND demonstrate potential for applications in theranostics with cancer therapy via the combination of local drug delivery and local hyperthermia, as well as for monitoring treatment effectiveness with fluorescence imaging.
authors.affiliation: Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato, Tokyo 105-8512, Japan. Electronic address: hiruta-yk@pha.keio.ac.jp.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hiruta
authors.affiliation: Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato, Tokyo 105-8512, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Nemoto
authors.affiliation: Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato, Tokyo 105-8512, Japan. Electronic address: kanazawa-hd@pha.keio.ac.jp.
authors.forename: Hideko
authors.initials: H
authors.lastname: Kanazawa
mesh_terms: D015195:Drug Design; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D006367:HeLa Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008856:Microscopy, Fluorescence; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D012822:Silicon Dioxide / Q000737:chemistry / Q000493:pharmacokinetics*; D013501:Surface-Active Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D013696:Temperature; D014407:Tumor Cells, Cultured
chemical_list: D005456:Fluorescent Dyes; D011108:Polymers; D013501:Surface-Active Agents; D012822:Silicon Dioxide
keywords: Cellular uptake; Fluorescence imaging; Hybrid material; Nanoparticle; Temperature-responsive polymer