Positive cooperativity in the cellular uptake of a boronated porphyrin

This work was undertaken to assess the kinetics of boronated porphyrin cellular uptake, which has been reported to occur by way of the low-density lipoprotein receptors. Because of current interest in the use of boronated porphyrins in boron neutron capture therapy of tumors, this pathway was investigated for the cellular uptake of a boronated porphyrin (tetrakis-carborane-carboxylate, esters of 2,4-bis (alpha,beta-dihydroxyethyl) deuteroporphyrin IX). Boron uptake occurred even without low-density lipoprotein in the culture medium. Pre-incubation of V-79 Chinese hamster cells for 24 h in medium containing delipidized fetal bovine serum markedly increased the subsequent uptake of boron when compared with cells pre-incubated with medium containing 10% fetal bovine serum. The increased uptake was characterized by greater affinity for boronated porphyrin, compared to cells pre-incubated in 10% fetal bovine serum. Twenty-four hour preincubation of cells with increasing concentrations of LDL added to delipidized medium suppressed the up-regulation of the boron level. In contrast, incubation with added acetylated LDL did not prevent the up-regulation of boron uptake. Positive cooperativity was demonstrated by Hill and Scatchard plots. It is concluded that uptake of boronated porphyrin is characterized by positive cooperativity, that its uptake is markedly enhanced when preincubated in delipidized serum, and that significant uptake occurs even in the absence of low density lipoprotein in the medium. These data suggest a novel way for enhancing uptake of boron (and perhaps other agents) into tissues using carrier porphyrins, by increasing the number and/or affinity of cellular LDL receptors.