The potential of transferrin-pendant-type polyethyleneglycol liposomes encapsulating decahydrodecaborate-(10)B (GB-10) as (10)B-carriers for boron neutron capture therapy.
OBJECTIVE
To evaluate GB-10-encapsulating transferrin (TF)-pendant-type polyethyleneglycol (PEG) liposomes as tumor-targeting (10)B-carriers for boron neutron capture therapy.


METHODS
A free mercaptoundecahydrododecaborate-(10)B (BSH) or decahydrodecaborate-(10)B (GB-10) solution, bare liposomes, PEG liposomes, or TF-PEG liposomes were injected into SCC VII tumor-bearing mice, and (10)B concentrations in the tumors and normal tissues were measured by gamma-ray spectrometry. Meanwhile, tumor-bearing mice were continuously given 5-bromo-2'-deoxyuridine (BrdU) to label all intratumor proliferating cells, then injected with these (10)B-carriers containing BSH or GB-10 in the same manner. Right after thermal neutron irradiation, the response of quiescent (Q) cells was assessed in terms of the micronucleus frequency using immunofluorescence staining for BrdU. The frequency in the total tumor cells was determined from the BrdU nontreated tumors.


RESULTS
Transferrin-PEG liposomes showed a prolonged retention in blood circulation, low uptake by reticuloendothelial system, and the most enhanced accumulation of (10)B in solid tumors. In general, the enhancing effects were significantly greater in total cells than Q cells. In both cells, the enhancing effects of GB-10-containing (10)B-carriers were significantly greater than BSH-containing (10)B-carriers, whether loaded in free solution or liposomes. In both cells, whether BSH or GB-10 was employed, the greatest enhancing effect was observed with TF-PEG liposomes followed in decreasing order by PEG liposomes, bare liposomes, and free BSH or GB-10 solution. In Q cells, the decrease was remarkable between PEG and bare liposomes.


CONCLUSIONS
In terms of biodistribution characteristics and tumor cell-killing effect as a whole, including Q cells, GB-10 TF-PEG liposomes were regarded as promising (10)B-carriers.
Masunaga
Shin-Ichiro
S
Particle Radiation Oncology Research Laboratory, Kyoto University, Kumatori, Osaka, Japan. smasuna@rri.kyoto-u.ac.jp
Kasaoka
Satoshi
S
Maruyama
Kazuo
K
Nigg
David
D
Sakurai
Yoshinori
Y
Nagata
Kenji
K
Suzuki
Minoru
M
Kinashi
Yuko
Y
Maruhashi
Akira
A
Ono
Koji
K
D000818:Animals; D001894:Borohydrides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001896:Boron Compounds / Q000008:administration & dosage*; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D001973:Bromodeoxyuridine; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000532:radiotherapy; D004337:Drug Carriers / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008081:Liposomes; D051379:Mice; D015162:Micronucleus Tests; D011092:Polyethylene Glycols; D013438:Sulfhydryl Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014168:Transferrin
D001894:Borohydrides; D001896:Boron Compounds; D004337:Drug Carriers; D008081:Liposomes; D013438:Sulfhydryl Compounds; D014168:Transferrin; C014651:mercaptoundecahydrododecaborate; D011092:Polyethylene Glycols; D001973:Bromodeoxyuridine