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 language | English |
|---|---|
| Pages (from-to) | 653-659 |
| Number of pages | 7 |
| Journal | Oncology Reports |
| Volume | 17 |
| Issue number | 3 |
| Publication status | Published - 2007 Mar |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - 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
AU - Oyama, Takahiko
AU - Kawamura, Masafumi
AU - Abiko, Tomohiro
AU - Izumi, Yotaro
AU - Watanabe, Masazumi
AU - Kumazawa, Eiji
AU - Kuga, Hiroshi
AU - Shiose, Yoshinobu
AU - Kobayashi, Koichi
PY - 2007/3
Y1 - 2007/3
N2 - 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.
AB - 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.
KW - Doxorubicin hydrochlorideconjugate
KW - Drug delivery system
KW - Hyperthermia
KW - Macromolecular carrier
KW - Non-small cell lung cancer
UR - http://www.scopus.com/inward/record.url?scp=34247853331&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34247853331&partnerID=8YFLogxK
M3 - Article
C2 - 17273747
AN - SCOPUS:34247853331
VL - 17
SP - 653
EP - 659
JO - Oncology Reports
JF - Oncology Reports
SN - 1021-335X
IS - 3
ER -