Hydrophobic boron compound-loaded poly(l-lactide-co-glycolide) nanoparticles for boron neutron capture therapy.

Poly(DL-lactide-co-glycolide) (PLGA) has been widely used and studied because of its biocompatibility and biodegradability. Recently, the usefulness of nanoparticles using poly(L-lactide-co-glycolide) (PLLGA) having a higher glass transition temperature than PLGA was suggested. In this study, we investigated the availability of boron compound-loaded PLGA and PLLGA nanoparticles for boron neutron capture therapy (BNCT) by conducting biodistribution study using tumor-bearing mice. o-Carborane, a hydrophobic boron compound, was used as a boron carrier, and o-carborane-albumin conjugate was used as a control. We prepared PLGA and PLLGA nanoparticles with diameters of 100nm and 150nm. In 100-nm PLLGA nanoparticles, the boron concentration in the tumor reached 113.9±15.8μg/g of tissue at 8h after administration. This result indicated that 100-nm PLLGA nanoparticles were able to achieve an intratumoral 10B concentration of 20μg/g without replacing the 11B with 10B. In addition, by nanoparticulation using PLGA7510 and PLLGA7510, intratumoral boron concentration was 1.7-3.2 and 3.5-4.2 times higher than that of the o-carborane-albumin conjugate, respectively. The tumor/blood ratios of boron concentration reached over 5 at 8-12h after injection. Boron atoms in nanoparticles were excreted mainly in the urine, and characteristic accumulation was not observed in other organs. These results suggested that 100-nm PLLGA nanoparticles were particularly useful for BNCT.