Boron neutron capture therapy (BNCT) is a binary
radiotherapy based on nuclear reactions that occur when
boron-10 is irradiated with neutrons, which result in the ejection of high-energy alpha particles. Successful BNCT requires the efficient delivery of a
boron-containing compound to effect high concentrations in
tumor cells while minimizing uptake in normal tissues. In this study, PEGylated
liposomes were employed as
boron carriers to maximize delivery to
tumors and minimize uptake in the reticuloendothelial system (RES). The water-soluble
potassium salt of nido-7,8-carborane,
nido-carborane, was chosen as the
boron source due to its high
boron content per molecule.
Nido-carborane was encapsulated in the aqueous cores of PEGylated
liposomes by hydrating thin
lipid films. Repeated freezing and thawing increased
nido-carborane loading by up to 47.5 ± 3.1%. The average hydrodynamic diameter of the prepared boronated
liposomes was determined to be 114.5 ± 28 nm through dynamic light scattering (DLS) measurement. Globular
liposomes approximately 100 nm in diameter were clearly visible in transmission electron microscope (TEM) images. The viability of
tumor cells following BNCT with 70 μM
nido-carborane was reduced to 17.1% compared to irradiated control cells, which did not contain boronated
liposomes. Confocal microscopy revealed that fluorescently labeled
liposomes injected into the tail veins of mice were deeply and evenly distributed in
tumor tissues and localized in the cytoplasm of
tumor cells. When mice were properly shielded with a 12 mm-thick
polyethylene board during in-vivo irradiation at a thermal neutron flux of 1.94 × 104/cm2·sec, almost complete
tumor suppression was achieved in
tumor models injected with boronated
liposomes (21.0 mg 10B/kg). Two BNCT cycles spaced 10 days apart further enhanced the therapeutic anti-
tumor effect, even when the dose was lowered to 10.5 mg 10B/kg. No notable
weight loss was observed in the
tumor models during the BNCT study.