Original boron cluster covalent with poly-zwitterionic BODIPYs for boron neutron capture therapy agent

Abstract

Currently, boron neutron capture therapy（BNCT） is the most innovative and promising highly selective targeted radiotherapy for cancer. Therefore, this paper designed and synthesized two kinds of boron-polymers, wrapped in the same fluorophore -BODIPYs, as fluorescent targeting markers for rapid, accurate, real-time, and inexpensive detection of boron-containing drugs. The spherical polymer o-carborane (PBC) in different polar solvents, the ultraviolet maximum absorption wavelength is in the range of 530–545 nm. The maximum ultraviolet absorption wavelength of PBD is in the range of 440–520 nm. The fluorescence spectra of the two boron-polymer are very similar, and the maximum emission wavelength is concentrated in the range of 550–560 nm. In terms of cytotoxicity and in vitro cell imaging, the in vitro biological toxicity evaluation of the two boron-polymer reached the expected high level, especially the cytotoxic concentration of PBD reached 1.347 ± 0.033 μM, which was higher than the 2.829 ± 0.351 μM of PBC. By transmission electron microscopy, it was found that the two terminal zwitterions of BODIPY polymer tightly wrapped boron clusters to form small particle nanoclusters. The imaging of the two boron-polymers was tested in the Hera cell lines of low, medium, and high densities. The in vitro study results revealed high levels of accumulation in HeLa cells with higher cytotoxicity and boron uptake compared to L-boron-phenylalanine (BPA). In vivo imaging, large number of borane polymers were observed to accumulate in the subcutaneous tumor sites of mice over time, indicating that it has high selectivity and high aggregation.