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NC‐6300, an epirubicin‐incorporating micelle, extends the antitumor effect and reduces the cardiotoxicity of epirubicin

Cancer science, 2013-07, Vol.104 (7), p.920-925 [Peer Reviewed Journal]

2013 Japanese Cancer Association ;2013 Japanese Cancer Association. ;Copyright John Wiley & Sons, Inc. Jul 2013 ;ISSN: 1347-9032 ;EISSN: 1349-7006 ;DOI: 10.1111/cas.12153 ;PMID: 23495762

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Title:
NC‐6300, an epirubicin‐incorporating micelle, extends the antitumor effect and reduces the cardiotoxicity of epirubicin
Author: Takahashi, Amane ; Yamamoto, Yoshiyuki ; Yasunaga, Masahiro ; Koga, Yoshikatsu ; Kuroda, Jun‐ichiro ; Takigahira, Misato ; Harada, Mitsunori ; Saito, Hiroyuki ; Hayashi, Tatsuyuki ; Kato, Yasuki ; Kinoshita, Taira ; Ohkohchi, Nobuhiro ; Hyodo, Ichinosuke ; Matsumura, Yasuhiro
Subjects: Animals ; Antibiotics, Antineoplastic - adverse effects ; Antibiotics, Antineoplastic - pharmacology ; Antineoplastic Agents - adverse effects ; Antineoplastic Agents - pharmacology ; Antitumor activity ; Bioluminescence ; Cancer ; Carcinoma, Hepatocellular - drug therapy ; Cardiotoxicity ; Cell culture ; Cell Line, Tumor ; Dosage ; Drug dosages ; Echocardiography ; Epirubicin ; Epirubicin - adverse effects ; Epirubicin - analogs & derivatives ; Epirubicin - pharmacology ; Female ; Heart - drug effects ; Hepatocellular carcinoma ; Humans ; Kinases ; Life sciences ; Liver ; Liver Neoplasms - drug therapy ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Nude ; Micelles ; Mortality ; Original ; Plasmids ; Proteins - adverse effects ; Proteins - pharmacology ; Random Allocation ; Tissue Distribution - drug effects ; Tumors ; Xenograft Model Antitumor Assays ; Xenografts
Is Part Of: Cancer science, 2013-07, Vol.104 (7), p.920-925
Description: Epirubicin is widely used to treat various human tumors. However, it is difficult to achieve a sufficient antitumor effect because of dosage limitation to prevent cardiotoxicity. We hypothesized that epirubicin‐incorporating micelle would reduce cardiotoxicity and improve the antitumor effect. NC‐6300 comprises epirubicin covalently bound to PEG polyaspartate block copolymer through an acid–labile hydrazone bond. The conjugate forms a micellar structure of 40–80 nm in diameter in an aqueous milieu. NC‐6300 (10, 15 mg/kg) and epirubicin (10 mg/kg) were given i.v. three times to mice bearing s.c. or liver xenograft of human hepatocellular carcinoma Hep3B cells. Cardiotoxicity was evaluated by echocardiography in C57BL/6 mice that were given NC‐6300 (10 mg/kg) or epirubicin (10 mg/kg) in nine doses over 12 weeks. NC‐6300 showed a significantly potent antitumor effect against Hep3B s.c. tumors compared with epirubicin. Moreover, NC‐6300 also produced a significantly longer survival rate than epirubicin against the liver orthotopic tumor of Hep3B. With respect to cardiotoxicity, epirubicin‐treated mice showed significant deteriorations in fractional shortening and ejection fraction. In contrast, cardiac functions of NC‐6300 treated mice were no less well maintained than in control mice. This study warrants a clinical evaluation of NC‐6300 in patients with hepatocellular carcinoma or other cancers.
Publisher: England: John Wiley & Sons, Inc
Language: English
Identifier: ISSN: 1347-9032
EISSN: 1349-7006
DOI: 10.1111/cas.12153
PMID: 23495762
Source: Wiley Blackwell Titles (Open access)

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NC‐6300, an epirubicin‐incorporating micelle, extends the antitumor effect and reduces the cardiotoxicity of epirubicin

2013 Japanese Cancer Association ;2013 Japanese Cancer Association. ;Copyright John Wiley & Sons, Inc. Jul 2013 ;ISSN: 1347-9032 ;EISSN: 1349-7006 ;DOI: 10.1111/cas.12153 ;PMID: 23495762

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