Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan.
Biomaterials. 2012 May;33(13):3568-77. doi: 10.1016/j.biomaterials.2012.01.039. Epub 2012 Feb 11.
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, (125)I (radioisotope)-labeled PM and NPM micelles were administered to colon-26 tumor-bearing BALB/c mice. The (125)I-labeled PM micelles showed prolonged blood circulation (area under the concentration curve (AUC): 943.4) than the (125)I-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.
核-壳型聚合物胶束（PM 胶束）是通过自由基共聚，由带有缩醛基和甲基丙烯酰基的聚乙二醇-聚乳酸嵌段共聚物（缩醛-PEG-b-PLA-MA）与 1-（4-乙烯基苄基）- closo-二硼烷（VB-二硼烷）反应得到的，并研究了这些胶束作为硼中子俘获治疗（BNCT）的肿瘤靶向硼递药系统的应用。非聚合胶束（NPM 胶束）物理包载 VB-二硼烷，在 37°C、10%胎牛血清（FBS）孵育 12 h 后，VB-二硼烷的漏出量约为 50%。而 PM 胶束即使孵育 48 h 后也没有漏出。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 胶束施用于结肠 26 荷瘤 BALB/c 小鼠。（125）I 标记的 PM 胶束表现出比（125）I 标记的 NPM 胶束更长的血液循环时间（浓度曲线下面积（AUC）：943.4）（AUC：495.1），而两种胶束的肿瘤积聚相似（AUC（PM 胶束）：249.6，AUC（NPM 胶束）：201.1）。相比之下，PM 胶束中硼物种的肿瘤积聚（AUC：268.6）是 NPM 胶束（AUC：37.1）的 7 倍，通过 ICP-AES 测定。热中子照射使接受 PM 胶束治疗的荷瘤小鼠的肿瘤生长受到抑制，而体重没有减轻。基于这些数据，PM 胶束为 BNCT 中硼载体的构建提供了一种很有前途的方法。
