Toward a Cancer Therapy with Boron-Rich Oligomeric Phosphate Diesters That Target the Cell Nucleus

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 96; no. 1; pp. 238 - 241
• Main Authors: Nakanishi, Akira, Guan, Lufeng, Kane, Robert R., Kasamatsu, Harumi, Hawthorne, M. Frederick
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 05.01.1999; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences
• Subjects: Biological Sciences; Biological Transport; Boron; Boron Compounds - metabolism; Boron Neutron Capture Therapy; Cancer; Cell Compartmentation; Cell lines; Cell membranes; Cell nucleus; Cell Nucleus - metabolism; Cells; Cytoplasm; Cytoplasm - metabolism; Fluoresceins - metabolism; Kidney cells; Medical research; Microinjections; Molecules; Neoplasms - therapy; Organophosphates - metabolism; Phosphates; Radiation; Therapy; Tumors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.96.1.238

The viability of boron neutron capture therapy depends on the development of tumor-targeting agents that contain large numbers of boron-10 (10B) atoms and are readily taken up by cells. Here we report on the selective uptake of homogeneous fluorescein-labeled nido-carboranyl oligomeric phosphate diesters (nido-OPDs) by the cell nucleus and their long-term retention after their delivery into the cytoplasm of TC7 cells by microinjection. All nido-OPDs accumulated in the cell nucleus within 2 h after microinjection. However, nido-OPDs in which the carborane cage was located on a side chain attached to the oligomeric backbone were redistributed between both the cytoplasm and nucleus after 24 h of incubation, whereas nido-OPDs in which the carborane cage was located along the oligomeric backbone remained primarily in the nucleus. Furthermore, cell-free incubation of digitonin-permeabilized TC7 cells with the nido-OPDs resulted in nuclear accumulation of the compounds, thus corroborating the microinjection studies. Our observation of fluorescence primarily located in the cell nucleus indicates that nuclear-specific uptake of sufficient amounts of10B for effective boron neutron capture therapy (≈ 108-109 10B atoms/tumor cell) via nido-OPDs is achievable.