Tumor-specific targeting of sodium borocaptate (BSH) to malignant glioma by transferrin-PEG liposomes: a modality for boron neutron capture therapy

被引：87

作者：

Doi, Atsushi ^{[1
]}

Kawabata, Shinji ^{[1
]}

Iida, Kyoko ^{[1
]}

Yokoyama, Kunio ^{[1
]}

Kajimoto, Yoshinaga ^{[1
]}

Kuroiwa, Toshihiko ^{[1
]}

Shirakawa, Takashi ^{[2
]}

Kirihata, Mitsunori ^{[2
]}

Kasaoka, Satoshi ^{[3
]}

Maruyama, Kazuo ^{[4
]}

Kumada, Hiroaki ^{[5
]}

Sakurai, Yoshinori ^{[6
]}

Masunaga, Shin-Ichiro ^{[6
]}

Ono, Koji ^{[6
]}

Miyatake, Shin-Ichi ^{[1
]}

机构：

[1] Osaka Med Coll, Dept Neurosurg, Osaka 5698686, Japan

[2] Osaka Prefecture Univ, Grad Sch Agr & Life Sci, Dept Appl Biochem, Osaka, Japan

[3] Hiroshima Int Univ, Fac Pharmaceut Sci, Kure, Japan

[4] Teikyo Univ, Dept Pharmaceut, Sagamihara, Kanagawa, Japan

[5] Japan Atom Energy Res Inst, Tokai Res Estab, Dept Res Reactor, Ibaraki, Japan

[6] Kyoto Univ, Inst Res Reactor, Res Lab, Osaka 59004, Japan

来源：

JOURNAL OF NEURO-ONCOLOGY | 2008年 / 87卷 / 03期

关键词：

malignant glioma; BNCT; transferrin-PEG liposome; BSH; ICP-AES;

D O I：

10.1007/s11060-008-9522-8

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Object Boron neutron capture therapy (BNCT) requires selective delivery of a high concentration of boron-10 (B-10) to tumor tissue. To improve a drug delivery in BNCT, we devised transferrin-conjugated polyethylene-glycol liposome encapsulating sodium borocaptate (TF-PEG-BSH). Methods B-10 concentrations of U87 Delta human glioma cells from three boron delivery systems (BDS) (bare BSH, PEG-BSH, and TF-PEG-BSH) were analyzed in vitro by use of inductively coupled plasma-atomic emission spectrometry (ICP-AES). A colony-forming assay (CFA) was performed using this cell line with the three BDS and neutron irradiation. Subcellular localization of BSH in tumor cells was analyzed in vitro by immunocytochemistry using monoclonal antibodies raised for BSH. Brain tumor models were made and the B-10 concentrations of the tumor, blood, and normal brain from each BDS were analyzed in vivo by use of ICP-AES. The tumor-to-blood and the tumor-to-normal brain ratios were evaluated. BNCT for the brain tumor models was performed and survival was analyzed. Results In CFA, TF-PEG-BSH showed the most prominent effects by neutron irradiation among the three BDS. TF-PEG-BSH showed highly selective and highly efficient B-10 delivery in tumor tissue. The survival rate in the treatment experiment was best in the TF-PEG-BSH group. Immunocytochemically, TF-PEG-BSH delivered BSH efficiently not only into the cytoplasm but also into the nucleus. Conclusion TF-PEG-BSH is a potent BDS for BNCT not only in terms of delivering a high concentration of B-10 into tumor tissue, but also the selective delivery of B-10 into the tumor cells.

引用

页码：287 / 294

页数：8

共 36 条

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