Amphiphilic Brush-Like Copolymers Involving Hydrophobic Amino Acid- and Oligopeptide-Side Chains for Optical Tumor Imaging In Vivo

• Koji Miki

  Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University

• Katsuya Nakano

  Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University

• Hideki Matsuoka

  Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University

• Chan Joo Yeom

  Group of Radiation and Tumor Biology, Career-Path Promotion Unit for Young Life Scientists, Kyoto University

• Hiroshi Harada

  Group of Radiation and Tumor Biology, Career-Path Promotion Unit for Young Life Scientists, Kyoto University

• Masahiro Hiraoka

  Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University

• Kouichi Ohe

  Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University

Abstract

Amphiphilic brush-like copolymers having simple amino acids or oligopeptides and poly(ethylene glycol) as side chains were synthesized via ring-opening metathesis polymerization and further transformations. All of the synthesized copolymers formed spherical self-assemblies in water and their hydrodynamic diameters were 100–250 nm, as measured by dynamic light scattering. Amphiphilic polymers bearing leucine and valine can form stable spherical self-assemblies in water because of the synergistic effects of intermolecular hydrogen bonding and hydrophobic interaction. The oligomerization of leucine moieties and capping with the proper length of fatty acyl groups at an N-terminus could significantly affect both the stability and fluorescence intensity of near-infrared fluorescent (NIRF) dye-containing polymeric self-assemblies. All of the self-assemblies consisting of leucine- and oligoleucine-grafted copolymers with a NIRF indocyanine green dye and hydrophilic targeting agents showed low cytotoxicity in cell viability tests. Furthermore, self-assemblies consisting of N-acetylleucine-grafted copolymers with strong fluorescence could visualize a tumor site with high-contrast in vivo, while low contrast images were obtained by utilizing oligoleucine-grafted self-assemblies because of their weak fluorescence. These results indicate that the precise control of both the number of leucine moieties and the length of the fatty acyl groups is important to produce highly functionalized tumor-targeting vehicles delivering a NIRF dye.

Journal

• Bulletin of the Chemical Society of Japan

  Bulletin of the Chemical Society of Japan 85 (12), 1277-1286, 2012-12-01

  Oxford University Press (OUP)

Keywords

• General Chemistry

Details

• CRID: 1360002219096877184
• NII Article ID: 130004153014
• DOI: 10.1246/bcsj.20120220
• ISSN: 13480634
• ISSN: 00092673
• Web Site: https://academic.oup.com/bcsj/article-pdf/85/12/1277/56274390/bcsj.20120220.pdf
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