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 chromatography column than most components of Photofrin II (PII) - the sensitizer used for photochemical treatment of cancer in the clinic. The Hp diesters were found to be less efficient than PII in sensitizing cells to photoinactivation. This was partly due to de-esterification of the Hp diesters by esterase activity in the serum. The de-esterification of the Hp diesters was highly dependent on the ester group, with Hp 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 diheptyl ester. Incubation of NHIK 3025 cells with these dyes showed that the Hp diesters were all partly located in extranuclear spots and partly 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 diesters and light.