Chitosan Coating Effect on Cellular Uptake of PLGA Nanoparticles for Boron Neutron Capture Therapy.

The usefulness of poly(lactide-co-glycolide) nanoparticles as a boron compound carrier for boron neutron capture therapy has been recently reported. In this study, chitosan-modified poly(DL-lactide-co-glycolide) (PLGA) nanoparticles were prepared to better facilitate the delivery of boron to the tumor. Chitosan hydroxypropyltrimonium chloride (CS), which can easily be modified for compatibility with PLGA nanoparticles, was used as chitosan. o-Carborane-loaded PLGA nanoparticles (bare nanoparticles) with a mean volume diameter of 111.4 ± 30.1 nm, and o-Carborane-loaded PLGA nanoparticles coated with CS (CS-coated nanoparticles) with a mean volume diameter of 113.6 ± 32.5 nm were prepared via an emulsion solvent evaporation method. Electrophoretic mobility was measured to calculate the particle surface charge number density of these particles; particle surface charge number densities of -1.91 mM and 20.8 mM were obtained for the bare and CS-coated nanoparticles, respectively. This result indicates that the particle surface was fully covered with CS. In vitro cellular uptake tests were carried out by using B16 melanoma cells. From the results of observation via confocal laser scanning microscopy, it was revealed that CS-coated nanoparticles existed around the cell nucleus, and were localized in the cytoplasm. Cellular uptakes of bare and CS-coated nanoparticles were quantitatively assessed by using fluorescence-activated cell sorting; the mean fluorescence intensity of CS-coated nanoparticles was three times higher than that of bare nanoparticles. The number of boron atoms in B16 melanoma cells was also investigated. Inductively coupled plasma atomic emission spectroscopy revealed that the number of boron atoms per cell of CS-coated nanoparticles was 1.8 times higher than that of bare nanoparticles. Based on these findings, we consider CS-coated nanoparticles to be suitable for boron neutron capture therapy.