Thermal Sensitive Liposomes Improve Delivery of Boronated Agents for Boron Neutron Capture Therapy

Boron neutron capture therapy (BNCT) has the potential to become a viable cancer treatment modality, but its clinical translation requires sufficient tumor boron delivery while minimizing nonspecific accumulation. Thermal sensitive liposomes (TSLs) were designed to have a stable drug payload at physiological temperatures but engineered to have high permeability under mild hyperthermia. We found that TSLs improved the tumor-specific delivery of boronophenylalanine (BPA) and boronated 2-nitroimidazole derivative B-381 in D54 glioma cells. Uniquely, the 2-nitroimidazole moiety extended the tumor retention of boron content compared to BPA. This is the first study to show the delivery of boronated compounds using TSLs for BNCT, and these results will provide the basis of future clinical trials using TSLs for BNCT.