Tumor-specific targeting of sodium borocaptate (BSH) to malignant glioma by transferrin-PEG liposomes: a modality for boron neutron capture therapy.
OBJECTIVE
Boron neutron capture therapy (BNCT) requires selective delivery of a high concentration of boron-10 ((10)B) to tumor tissue. To improve a drug delivery in BNCT, we devised transferrin-conjugated polyethylene-glycol liposome encapsulating sodium borocaptate (TF-PEG-BSH).


METHODS
(10)B concentrations of U87Delta 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 (10)B 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 (10)B 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.


CONCLUSIONS
TF-PEG-BSH is a potent BDS for BNCT not only in terms of delivering a high concentration of (10)B into tumor tissue, but also the selective delivery of (10)B into the tumor cells.
Doi
Atsushi
A
Department of Neurosurgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan.
Kawabata
Shinji
S
Iida
Kyoko
K
Yokoyama
Kunio
K
Kajimoto
Yoshinaga
Y
Kuroiwa
Toshihiko
T
Shirakawa
Takashi
T
Kirihata
Mitsunori
M
Kasaoka
Satoshi
S
Maruyama
Kazuo
K
Kumada
Hiroaki
H
Sakurai
Yoshinori
Y
Masunaga
Shin-Ichiro
S
Ono
Koji
K
Miyatake
Shin-Ichi
S
D000818:Animals; D001894:Borohydrides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D001932:Brain Neoplasms / Q000532:radiotherapy*; D016503:Drug Delivery Systems; D005910:Glioma / Q000532:radiotherapy*; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011092:Polyethylene Glycols / Q000008:administration & dosage; D013054:Spectrophotometry, Atomic; D013438:Sulfhydryl Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014168:Transferrin / Q000008:administration & dosage
D001894:Borohydrides; D008081:Liposomes; D013438:Sulfhydryl Compounds; D014168:Transferrin; C014651:mercaptoundecahydrododecaborate; D011092:Polyethylene Glycols