Pharmacokinetics of core-polymerized, boron-conjugated micelles designed for boron neutron capture therapy for cancer
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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. 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 (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.
収録刊行物
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- Biomaterials
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Biomaterials 33 (13), 3568-3577, 2012-05
Elsevier
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詳細情報 詳細情報について
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- CRID
- 1050001202624728064
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- NII論文ID
- 120007130664
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- NII書誌ID
- AA00110092
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- ISSN
- 01429612
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- HANDLE
- 2241/116985
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- 本文言語コード
- en
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- 資料種別
- journal article
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- データソース種別
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- IRDB
- CiNii Articles