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

12 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

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Non-Small Cell Lung Carcinoma
Doxorubicin
Fever
Neoplasms
Drug Delivery Systems

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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

In: Oncology Reports, Vol. 17, No. 3, 03.2007, p. 653-659.

Research output: Contribution to journalArticle

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, vol. 17, no. 3, pp. 653-659.
Oyama, Takahiko ; Kawamura, Masafumi ; Abiko, Tomohiro ; Izumi, Yotaro ; Watanabe, Masazumi ; Kumazawa, Eiji ; Kuga, Hiroshi ; Shiose, Yoshinobu ; Kobayashi, Koichi. / 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. In: Oncology Reports. 2007 ; Vol. 17, No. 3. pp. 653-659.
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AU - Watanabe, Masazumi

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