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.