title: Preparation of immunostimulatory single-walled carbon nanotube/CpG DNA complexes and evaluation of their potential in cancer immunotherapy.
abstract: Carbon nanotubes (CNTs) have many interesting properties. In particular, their photohyperthermic effect by near-infrared (NIR) irradiation could be used to kill cancer cells, and could thus be applied in photohyperthermic therapy. However, the solubility of CNTs must be improved before they can be used in biological applications. As DNA is reported to disperse the CNTs in aqueous solution with π-π interactions, we hypothesis that immunostimulatory CpG DNA may also disperse the CNTs in aqueous solution. In this study, we used CpG DNA to disperse single-walled CNTs (SWCNTs) in aqueous solution, in order to combine photohyperthermic effect and immunoactivation together to achieve a more effective cancer therapy. As expected, CpG DNA effectively dispersed the SWCNTs in aqueous solution via the formation of SWCNT/CpG DNA complexes. Moreover, the immunoreactivity of the SWCNT/CpG DNA complexes was investigated. The results showed that intratumoral administration of the SWCNT/CpG DNA complexes in mice enhanced the production level of inflammatory cytokines in tumor tissues. Finally, we evaluated the antitumor effects of the SWCNT/CpG DNA complexes in tumor-bearing mice. The result indicated that intratumoral administration of the SWCNT/CpG DNA complexes combined with NIR irradiation was a more effective approach to prevent the proliferation of tumor growth.
authors.affiliation: Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan; The Japan Society for the Promotion of Science (JSPS), Chiyoda-ku, Tokyo 102-8471, Japan.
authors.forename: Shuwen
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Hashida
authors.affiliation: Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kawakami
authors.affiliation: Department of Molecular Engineering, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Kyoto 615-8510, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Mihara
authors.affiliation: Department of Molecular Engineering, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Kyoto 615-8510, Japan.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Umeyama
authors.affiliation: Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan; Department of Molecular Engineering, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Kyoto 615-8510, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Imahori
authors.affiliation: Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Murakami
authors.affiliation: Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Yamashita
authors.affiliation: Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan; Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. Electronic address: hashidam@pharm.kyoto-u.ac.jp.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Hashida
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology / Q000628:therapy*; D016207:Cytokines / Q000097:blood / Q000276:immunology; D004337:Drug Carriers / Q000737:chemistry*; D006358:Hot Temperature; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D008807:Mice, Inbred BALB C; D018625:Microscopy, Atomic Force; D037742:Nanotubes, Carbon / Q000737:chemistry*; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D019265:Spectroscopy, Near-Infrared; D013499:Surface Properties
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D016207:Cytokines; D004337:Drug Carriers; D037742:Nanotubes, Carbon; D009838:Oligodeoxyribonucleotides
keywords: Cancer; Carbon nanotubes; CpG DNA; Immune activation; Photohyperthermia