Mechanism of uptake of sulfonated metallophthalocyanines by cultured mammalian cells.

The uptake of several metallophthalocyanine tetrasulfonates by cultured Chinese hamster cells was studied. Uranyl- and chloraluminium were taken up at the highest rate followed by Ni-, Zn-, Cu-, Co- and dichlorosilicon-phthalocyanine tetrasulfonate. The uptake from the growth medium containing 10% serum in which only 15% of the dye is not bound to serum proteins was 5--18-fold slower than in the absence of serum, suggesting that most of the uptake is of free dye. Using gel filtration to separate tightly protein-bound dye from the free dye, binding curves were constructed that varied in slope and saturation values for the different compounds. At saturation, the number of dye molecules bound per serum albumin molecule varied from 1 for vanadyl- and cobalt-, to 4 for uranyl-phthalocyanine tetrsulfonate. Absorption spectra of the various phthalocyanines indicated that under physiological conditions, all dyes, with the exception of chloroaluminum- and dichlorosilicon-phthalocyanine tetrasulfonate, were aggregated. The rate of uptake was unrelated to the state of aggregation. The rate of uptake was temperature dependent at intervals longer than 1 h. At shorter times, very little temperature dependence was observed. These results suggest that the uptake process takes place in two steps. The first step is passive, involving binding of metallophthalocyanine tetrasulfonate to a receptor on the cell membrane, while the second one is active and involves internalization of the bound dye.