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Novel SN-38–Incorporated Polymeric Micelle, NK012, Strongly Suppresses Renal Cancer Progression

¹ Department of Urology, National Defense Medical College, Tokorozawa, Saitama, Japan; ² Shien-Lab, Medical Oncology, National Cancer Center Hospital; ³ National Cancer Center, Tokyo, Japan; and ⁴ Investigative Treatment Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Chiba, Japan

Requests for reprints: Yasuhiro Matsumura, Investigative Treatment Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa City, Chiba 277-8577, Japan. Phone: 81-4-7134-6857; Fax: 81-4-7134-6857; E-mail: yhmatsum{at}east.ncc.go.jp.

Key Words: drug delivery system • micelle • RCC

It has been recently reported that NK012, a 7-ethyl-10-hydroxy-camptothecin (SN-38)–releasing nanodevice, markedly enhances the antitumor activity of SN-38, especially in hypervascular tumors through the enhanced permeability and retention effect. Renal cell carcinoma (RCC) is a typical hypervascular tumor with an irregular vascular architecture. We therefore investigated the antitumor activity of NK012 in a hypervascular tumor model from RCC. Immunohistochemical examination revealed that Renca tumors contained much more CD34-positive neovessels than SKRC-49 tumors. Compared with CPT-11, NK012 had significant antitumor activity against both bulky Renca and SKRC-49 tumors. Notably, NK012 eradicated rapid-growing Renca tumors in 6 of 10 mice, whereas it failed to eradicate SKRC-49 tumors. In the pulmonary metastasis treatment model, an enhanced and prolonged distribution of free SN-38 was observed in metastatic lung tissues but not in nonmetastatic lung tissues after NK012 administration. NK012 treatment resulted in a significant decrease in metastatic nodule number and was of benefit to survival. Our study shows the outstanding advantage of polymeric micelle-based drug carriers and suggests that NK012 would be effective in treating disseminated RCCs with irregular vascular architectures. [Cancer Res 2008;68(6):1631–5]

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