Transferrin-Loaded nido-Carborane Liposomes:Tumor-Targeting Boron Delivery System for Neutron Capture Therapy

摘要

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 ~(125)I-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.