Novel SN-38-incorporated polymeric micelle, NK012, strongly suppresses renal
Author: Sumitomo M, Koizumi F, Asano T, Horiguchi A, Ito K, Asano T, Kakizoe T, Hayakawa M, Matsumura Y.
Journal: Cancer Res. 2008 Mar 15;68(6):1631-5.
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.
ナノテクで高分子ミセルに抗がん剤を入れると血管新生に富むRCC肺転移モデルによく効いたという内容。Drug delivery systemという意味で高分子ミセルは決して新しい話題ではないが、この論文では薬剤の組織滞在時間がミセル化で高まっているのでは、という考察があり面白い。
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