Novel SN-38-incorporated polymeric micelle, NK012, strongly suppresses renal cancer progression.
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.
Sumitomo
Makoto
M
Department of Urology, National Defense Medical College, Tokorozawa, Saitama, Japan.
Koizumi
Fumiaki
F
Asano
Takako
T
Horiguchi
Akio
A
Ito
Keiichi
K
Asano
Tomohiko
T
Kakizoe
Tadao
T
Hayakawa
Masamichi
M
Matsumura
Yasuhiro
Y
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D000077146:Irinotecan; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D011355:Prodrugs / Q000737:chemistry / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; D008823:Micelles; D011355:Prodrugs; D000077146:Irinotecan; D002166:Camptothecin