Micah John Luderer1, Barbara Muz1, Kinan Alhallak1,2, Jennifer Sun1,2, Katherine Wasden1, Nicole Guenthner1, Pilar de la Puente1, Cinzia Federico1, Abdel Kareem Azab3,4. 1. Department of Radiation Oncology, Cancer Biology Division, Washington University School of Medicine, 4511 Forest Park Ave., Room 3103, St. Louis, MO, 63108, USA. 2. Department of Biomedical Engineering, Washington University, St. Louis, MO, USA. 3. Department of Radiation Oncology, Cancer Biology Division, Washington University School of Medicine, 4511 Forest Park Ave., Room 3103, St. Louis, MO, 63108, USA. kareem.azab@wustl.edu. 4. Department of Biomedical Engineering, Washington University, St. Louis, MO, USA. kareem.azab@wustl.edu.
Abstract
PURPOSE: 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. METHODS: Thermal sensitive liposomes (TSLs) were designed to have a stable drug payload at physiological temperatures but engineered to have high permeability under mild hyperthermia. RESULTS: 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. CONCLUSION: 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.
PURPOSE:Boron neutron capture therapy (BNCT) has the potential to become a viable cancer treatment modality, but its clinical translation requires sufficient tumorboron delivery while minimizing nonspecific accumulation. METHODS: Thermal sensitive liposomes (TSLs) were designed to have a stable drug payload at physiological temperatures but engineered to have high permeability under mild hyperthermia. RESULTS: 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. CONCLUSION: 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.
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