Nakanishi A, Guan L, Kane R R, Kasamatsu H, Hawthorne M F
Department of Molecular, Cell, and Developmental Biology and the Molecular Biology Institute, University of California, 405 Hilgard Avenue, Los Angeles, CA 90095, USA.
Proc Natl Acad Sci U S A. 1999 Jan 5;96(1):238-41. 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 of 10B for effective boron neutron capture therapy ( approximately 10(8)-10(9) 10B atoms/tumor cell) via nido-OPDs is achievable.
硼中子俘获疗法的可行性取决于能否开发出含有大量硼 - 10（¹⁰B）原子且能被细胞轻易摄取的肿瘤靶向剂。在此，我们报告了均匀荧光素标记的巢式碳硼烷低聚磷酸二酯（nido - OPDs）被细胞核选择性摄取的情况，以及通过显微注射将其递送至TC7细胞细胞质后它们的长期留存情况。显微注射后2小时内，所有nido - OPDs都在细胞核中积累。然而，孵育24小时后，碳硼烷笼位于连接至低聚主链的侧链上的nido - OPDs在细胞质和细胞核之间重新分布，而碳硼烷笼沿着低聚主链定位的nido - OPDs主要仍留在细胞核中。此外，用nido - OPDs对洋地黄皂苷通透的TC7细胞进行无细胞孵育导致这些化合物在细胞核中积累，从而证实了显微注射研究。我们观察到荧光主要位于细胞核中，这表明通过nido - OPDs实现有效硼中子俘获疗法所需的足够量的¹⁰B（约10⁸ - 10⁹个¹⁰B原子/肿瘤细胞）的细胞核特异性摄取是可行的。
