Pharmacokinetics of core-polymerized, boron-conjugated micelles designed for boron neutron capture therapy for cancer.
Pharmacokinetics of core-polymerized, boron-conjugated micelles designed for boron neutron capture therapy for cancer.
复制标题
DOI：
10.1016/j.biomaterials.2012.01.039
复制
发表时间：
2012-05
期刊：
影响因子：
14
通讯作者：
S. Sumitani;Motoi Oishi;Tatsuya Yaguchi;Hiroki Murotani;Y. Horiguchi;Minoru Suzuki;K. Ono;H. Yanagie;Y. Nagasaki
中科院分区：
文献类型：
--
作者：
S. Sumitani;Motoi Oishi;Tatsuya Yaguchi;Hiroki Murotani;Y. Horiguchi;Minoru Suzuki;K. Ono;H. Yanagie;Y. Nagasaki
以1-（4-乙烯基苄基）-氯代碳硼烷（VB-carborane）为原料，通过自由基共聚反应制备了含缩醛基和甲基丙烯酰基的聚乙二醇-b-聚乳酸嵌段共聚物（缩醛-PEG-b-PLA-MA）和硼共轭胶束（PM胶束），并研究了PM胶束作为硼中子俘获治疗（BNCT）靶向给药系统的应用。物理掺入VB-碳硼烷的非聚合胶束（NPM胶束）显示出VB-碳硼烷的显著泄漏（约100%）。50%）。另一方面，甚至在孵育48小时后也没有观察到PM胶束的泄漏。为了阐明胶束的药代动力学，将125 I（放射性同位素）标记的PM和NPM胶束施用至结肠-26荷瘤BALB/c小鼠。125 I标记的PM胶束显示出比125 I标记的NPM胶束（AUC：495.1）延长的血液循环（浓度曲线下面积（AUC）：943.4），而两种类型的胶束的肿瘤蓄积相似（AUCPM胶束：249.6，AUCNPM胶束：201.1）。相比之下，通过ICP-AES测定，PM胶束中硼物质的肿瘤蓄积（AUC：268.6）比NPM胶束（AUC：37.1）高7倍。热中子照射产生的肿瘤生长抑制荷瘤小鼠与PM胶束治疗体重没有减少。在这些数据的基础上，PM胶束代表了一个有前途的方法来创建BNCT的硼载体。
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 h incubation with 10% fetal bovine serum (FBS) at 37 °C. On the other hand, no leakage from the PM micelles was observed even after 48 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. The125I-labeled PM micelles showed prolonged blood circulation (area under the concentration curve (AUC): 943.4) than the125I-labeled NPM micelles (AUC: 495.1), whereas tumor accumulation was similar for both types of micelles (AUCPM micelle: 249.6, AUCNPM 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.