PHOTOBIOLOGICAL PROPERTIES OF HEMATOPORPHYRIN DIESTERS - EVALUATION FOR POSSIBLE APPLICATION IN PHOTOCHEMOTHERAPY OF CANCER

The dimethyl, diethyl, dipropyl, dibutyl, diamyl, dihexyl and diheptyl esters of hematoporphyrin (Hp) were synthesized and shown to be more strongly retained on a reverse phase (C18) high performance liquid chr omatography column than most components of Photofrin II (PII) - the se nsitizer used for photochemical treatment of cancer in the clinic. The Hp diesters were found to be less efficient than PII in sensitizing c ells to photoinactivation. This was partly due to de-esterification of the Hp diesters by esterase activity in the serum. The de-esterificat ion of the Hp diesters was highly dependent on the ester group, with H p dimethyl ester (t1/2 for conversion to Hp monomethyl ester was 6 min ) being de-esterified with a rate 500 times faster than that for Hp di heptyl ester. Incubation of NHIK 3025 cells with these dyes showed tha t the Hp diesters were all partly located in extranuclear spots and pa rtly diffusely distributed in the cytoplasm. The fluorescing spots may be due to lysosomally located Hp diesters, since the lysosomal marker enzyme beta-Nacetyl-D-glucosaminidase was partly inactivated by Hp di esters and light.