Hyperthermia-enhanced tumor accumulation and antitumor efficacy of a doxorubicin-conjugate with a novel macromolecular carrier system in mice with non-small cell lung cancer

Takahiko Oyama, Masafumi Kawamura, Tomohiro Abiko, Yotaro Izumi, Masazumi Watanabe, Eiji Kumazawa, Hiroshi Kuga, Yoshinobu Shiose, Koichi Kobayashi

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

A novel drug delivery system (DDS) compound was formed by binding doxorubicin hydrochloride (DXR) to the macromolecular carrier carboxymethyldextran polyalcohol (CM-Dex-PA) via the peptidyl spacer (GGFG: Gly-Gly-Phe-Gly). Its use in a murine tumor model confirmed that the DDS (CM-Dex-PA-GGFG-DXR) was retained in the blood and distributed in tumor tissue. The combined use of hyperthermia (HT: 41-42°C for 40 min) and DXR-conjugate (5, 10 or 20 mg/kg i.v.) on tumor accumulation and efficacy was investigated in a murine model of non-small cell lung cancer. Tumor size was measured and the tumor inhibition rate (IR) was calculated. The mean tumor concentration of conjugated DXR in the DXR-conjugate group was 9.40 μg/g compared with 19.04 μg/g in the DXR-conjugate + HT group (p=0.0008). The antitumor efficacy of the DXR-conjugate was significantly enhanced in the groups receiving the combination therapy (p=0.0039, p=0.0250). Significant differences were found between the groups given DXR and those given DXR-conjugate (p=0.0492, p=0.0104). The results demonstrate that the antitumor efficacy of DXR-conjugate is significantly superior to that of DXR alone and the combined use of DXR-conjugate and HT increases the drug's concentration in the tumor, with significant enhancement of antitumor efficacy.

Original languageEnglish
Pages (from-to)653-659
Number of pages7
JournalOncology reports
Volume17
Issue number3
Publication statusPublished - 2007 Mar 1

Keywords

  • Doxorubicin hydrochlorideconjugate
  • Drug delivery system
  • Hyperthermia
  • Macromolecular carrier
  • Non-small cell lung cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Oyama, T., Kawamura, M., Abiko, T., Izumi, Y., Watanabe, M., Kumazawa, E., Kuga, H., Shiose, Y., & Kobayashi, K. (2007). Hyperthermia-enhanced tumor accumulation and antitumor efficacy of a doxorubicin-conjugate with a novel macromolecular carrier system in mice with non-small cell lung cancer. Oncology reports, 17(3), 653-659.