Transferrin-loaded nido-carborane liposomes: Tumor-targeting boron delivery system for neutron capture therapy

Authors:   Yusuke Miyajima,Hiroyuki Nakamura,Yasuhiro Kuwata,Jong Lee,Shinichiro Masunaga,Koji Ono,Kazuo Maruyama
Journal: Bioconjugate Chemistry
https://doi.org/10.1021/bc060064k
Abstract: The nido-carborane lipid 2 as a double-tailed boron lipid was synthesized from heptadecanol in five steps. The lipid 2 formed stable liposomes at 25% molar ratio toward DSPC with cholesterol. Transferrin was able to be introduced on the surface of boron liposomes (Tf(+)-PEG-CL liposomes) by the coupling of transferrin to the PEG-CO 2H moieties of Tf(-)-PEG-CL liposomes. The biodistribution of Tf(+)-PEG-CL liposomes, in which 125I-tyraminyl inulins were encapsulated, showed that Tf(+)-PEG-CL liposomes accumulated in tumor tissues and stayed there for a sufficiently long time to increase tumor/blood concentration ratio, although Tf(-)-PEG-CL liposomes were gradually released from tumor tissues with time. A boron concentration of 22 ppm in tumor tissues was achieved by the injection of Tf(+)-PEG-CL liposomes at 7.2 mg/kg body weight boron in tumor-bearing mice. After neutron irradiation, the average survival rate of mice not treated with Tf(+)-PEG-CL liposomes was 21 days, whereas that of the treated mice was 31 days. Longer survival rates were observed in the mice treated with Tf(+)-PEG-CL liposomes; one of them even survived for 52 days after BNCT. {textcopyright} 2006 American Chemical Society.