Synergistic electrochemotherapy on cancer cells by photodynamically active cytostatic agents

Two reliable methods have been combined: i) the electroporation of the cell membranes for facilitating the sensitizer incorporation into hystiocytic human lymphoma cells U-937 and (ii) the photodynamics applied by excitation of natural and synthetic sensitizers for cancer therapy. In the case of cytostatic sensitizers as daunomycin or actinomycin their photooxidation of guanine in DNA was added to their known dark medical efficacy for the first time. Several applications of single d.c. pulses and continuous visible light irradiations were performed, which resulted in about five times higher efficacy by 14 min of irradiation after the electroporation than the ordinary photodynamic effect itself on intact cell membranes. Yielding about 90% killing rate by a combination of electroporation and photooxidation this synergism will be the basis of an extended electrochemotherapy by light irradiation according to the photodynamic mechanism type 1 for the treatment of malignant cells and tissues. Analogous results--including the first synergistic treatment of tumor mice according to photodynamic mechanism type 2--were discussed, too.