Novel SN-38-incorporated polymeric micelle, NK012, strongly suppresses renal cancer progression

Makoto Sumitomo, Fumiaki Koizumi, Takako Asano, Akio Horiguchi, Keiichi Ito, Tomohiko Asano, Tadao Kakizoe, Masamichi Hayakawa, Yasuhiro Matsumura

Research output: Contribution to journalArticlepeer-review

55 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1631-1635
Number of pages5
JournalCancer Research
Volume68
Issue number6
DOIs
Publication statusPublished - 15-03-2008

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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