Photodynamic efficiency of liposome-administered tetramethyl hematoporphyrin in two human bladder cancer cell lines.
The main problems presented by superficial bladder carcinoma, its high recurrence rate and multifocal appearance, require treatment of the bladder as a whole. Photodynamic therapy (PDT) is one such experimental treatment for superficial bladder carcinoma, involving the administration of a photosensitizer that accumulates in the tumor tissue, and subsequent irradiation of the tumor with light. Since the photosensitizers used in PDT suffer from several drawbacks, new photosensitizers are being sought. Drug delivery systems are also being investigated for the administration of hydrophobic photosensitizers and enhancement of photodynamic efficiency and tumor selectivity. In this study we examined a new photosensitizer, tetramethyl hematoporphyrin (TMHP), in two human bladder cancer cell lines. In the first pair of the experiments, TMHP was bound to unilamellar liposomes. Cellular uptake, dark toxicity and photodynamic efficiency were then studied. Fluorescence microscopy showed TMHP localization in the cytoplasm in a perinuclear region, sparing the nucleus. Dark toxicity occurred after incubation of cells with TMHP above a concentration of 20 micrograms/ml. Irradiation was carried out using an argon-pumped dye laser emitting a wavelength of 630 nm at a fluence of 3.6 and 7.2 J/cm2. Before irradiation, cells were incubated with TMHP at concentrations of 2.5 and 5 micrograms/ml for 1 h. Cell survival rates after incubation with 5 micrograms/ml TMHP and irradiation at 7.2 J/cm2 were 15.7% of control cells for Rec and 4.5% for Waf cells. Uptake studies showed a higher intracellular TMHP concentration in Waf than in Rec cells. This correlates with the higher PDT efficiency seen in Waf cells.(ABSTRACT TRUNCATED AT 250 WORDS)
D002295:Carcinoma, Transitional Cell / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D002470:Cell Survival; D006415:Hematoporphyrins / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D008081:Liposomes; D008856:Microscopy, Fluorescence; D010778:Photochemotherapy; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D006415:Hematoporphyrins; D008081:Liposomes; C096503:tetramethyl hematoporphyrin