Synthesis and cellular studies of polyamine conjugates of a mercaptomethyl–carboranylporphyrin

Seven polyamine conjugates of a tri(p-carboranylmethylthio)tetrafluorophenylporphyrin were prepared in high yields by sequential substitution of the p-phenyl fluoride of tetrakis(pentafluorophenyl)porphyrin (TPPF), and investigated as boron delivery agents for boron neutron capture therapy (BNCT). The polyamines used were derivatives of the natural-occurring spermine with different lengths of the carbon chains, terminal primary amine groups and, in two of the conjugates, additional aminoethyl moieties. A tri(polyethylene glycol) conjugate was also synthesized for comparison purposes. The polyamine conjugates showed low dark cytotoxicity (IC50 >400 μM) and low phototoxicity (IC50 >40 μM at 1.5 J/cm2). All polyamine conjugates, with one exception, showed higher uptake into human glioma T98G cells (up to 12-fold) than the PEG conjugate, and localized preferentially in the cell ER, Golgi and the lysosomes. Our results show that spermine derivatives can serve as effective carriers of boronated porphyrins for the BNCT of tumors.

Boron-containing spermine–porphyrin conjugates are promising boron neutron capture therapy agents because they are efficiently taken up by human glioma T98G cells and show very low cytotoxicities.Figure optionsDownload as PowerPoint slide