Novel SN-38–Incorporating Polymeric Micelles, NK012, Eradicate Vascular Endothelial Growth Factor–Secreting Bulky Tumors

DOI PDF 被引用文献26件
  • Fumiaki Koizumi
    1Investigative Treatment Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan;
  • Masayuki Kitagawa
    2Pharmaceutical Research Laboratories, Research and Development Group, Nippon Kayaku Co., Ltd, Kita-ku, Tokyo, Japan; and
  • Takahito Negishi
    1Investigative Treatment Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan;
  • Takeshi Onda
    2Pharmaceutical Research Laboratories, Research and Development Group, Nippon Kayaku Co., Ltd, Kita-ku, Tokyo, Japan; and
  • Shin-ichi Matsumoto
    2Pharmaceutical Research Laboratories, Research and Development Group, Nippon Kayaku Co., Ltd, Kita-ku, Tokyo, Japan; and
  • Tetsuya Hamaguchi
    3Department of Medicine, National Cancer Center Hospital, Tyuo-ku, Tokyo, Japan
  • Yasuhiro Matsumura
    1Investigative Treatment Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan;

抄録

<jats:title>Abstract</jats:title> <jats:p>7-Ethyl-10-hydroxy-camptothecin (SN-38), a biological active metabolite of irinotecan hydrochloride (CPT-11), has potent antitumor activity but has not been used clinically because it is a water-insoluble drug. For delivery by i.v. injection, we have successfully developed NK012, a SN-38-releasing nanodevice. The purpose of this study is to investigate the pharmacologic character of NK012 as an anticancer agent, especially in a vascular endothelial growth factor (VEGF)–secreting tumor model. The particle size of NK012 was ∼20 nm with a narrow size distribution. NK012 exhibited a much higher cytotoxic effect against lung and colon cancer cell lines as compared with CPT-11. NK012 showed significantly potent antitumor activity against a human colorectal cancer HT-29 xenograft as compared with CPT-11. Enhanced and prolonged distribution of free SN-38 in the tumor was observed after the injection of NK012. NK012 also had significant antitumor activity against bulky SBC-3/Neo (1,533.1 ± 1,204.7 mm3) and SBC-3/VEGF tumors (1,620.7 ± 834.0 mm3) compared with CPT-11. Furthermore, NK012 eradicated bulky SBC-3/VEGF tumors in all mice but did not eradicate SBC-3/Neo tumors. In the drug distribution analysis, an increased accumulation of SN-38 in SBC-3/VEGF tumors was observed as compared with that in SBC-3/Neo tumors. NK012 markedly enhanced the antitumor activity of SN-38, especially in highly VEGF-secreting tumors, and could be a promising SN-38-based formulation. (Cancer Res 2006; 66(20): 10048-56)</jats:p>

収録刊行物

  • Cancer Research

    Cancer Research 66 (20), 10048-10056, 2006-10-15

    American Association for Cancer Research (AACR)

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