Pharmacokinetics of core-polymerized, boron-conjugated micelles designed for boron neutron capture therapy for cancer

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• 作者：Shogo Sumitani^a ; Motoi Oishi^a ; Tatsuya Yaguchi^a ; Hiroki Murotani^a ; Yukichi Horiguchi^a ; Minoru Suzuki^d ; Koji Ono^d ; Hironobu Yanagie^e ; Yukio Nagasaki^a ; ^b ; ^c ; ^{yukio@nagalabo.jp}
• 关键词：Boron neutron capture therapy ; Poly(ethylene glycol)-block-poly(lactic acid) copolymer ; Polymeric micelles ; Drug delivery systems ; Biodistribution ; Nanoparticle-assisted BNCT
• 刊名：Biomaterials
• 出版年：2012
• 期刊代码：7_01429612
• 类别：ms
• 出版时间：May, 2012
• 卷：33
• 期：13
• 页码：3568-3577
• 文件大小：1332 K

摘要

Core-polymerized and boron-conjugated micelles (PM micelles) were prepared by free radical copolymerization of a PEG-b-PLA block copolymer bearing an acetal group and a methacryloyl group (acetal-PEG-b-PLA-MA), with 1-(4-vinylbenzyl)-closo-carborane (VB-carborane), and the utility of these micelles as a tumor-targeted boron delivery system was investigated for boron neutron capture therapy (BNCT). Non-polymerized micelles (NPM micelles) that incorporated VB-carborane physically showed significant leakage of VB-carborane (ca. 50%) after 12聽h incubation with 10%fetal bovine serum (FBS) at 37聽掳C. On the other hand, no leakage from the PM micelles was observed even after 48聽h of incubation. To clarify the pharmacokinetics of the micelles, ¹²⁵I (radioisotope)-labeled PM and NPM micelles were administered to colon-26 tumor-bearing BALB/c mice. The ¹²⁵I-labeled PM micelles showed prolonged blood circulation (area under the concentration curve (AUC): 943.4) than the ¹²⁵I-labeled NPM micelles (AUC: 495.1), whereas tumor accumulation was similar for both types of micelles (AUC_{PM micelle}: 249.6, AUC_{NPM micelle}: 201.1). In contrast, the tumor accumulation of boron species in the PM micelles (AUC: 268.6) was 7-fold higher than the NPM micelles (AUC: 37.1), determined by ICP-AES. Thermal neutron irradiation yielded tumor growth suppression in the tumor-bearing mice treated with the PM micelles without reduction in body weight. On the basis of these data, the PM micelles represent a promising approach to the creation of boron carrier for BNCT.