chlorophyll-a and Urinary-Bladder-Neoplasms

Topics: Animals; Chlorophyll; Gold; Iron; Mice; Nanotubes; Photochemotherapy; Photosensitizing Agents; Surface-Active Agents; Triazenes; Urinary Bladder Neoplasms

To assess the efficacy of chlorophyll derivative (CPD4)-Photodynamic therapy (PDT) in preventing postoperative recurrence of the infiltrative cancer of the urinary bladder.. Thirty-two patients were treated with CPD4-PDT postoperationally to prevent the recurrence of cancer, all of which being followed up.. The recurrence rate was 42.1% in T2 tumors and 69.2% in T3 tumors (P < 0.05), and the survival period without tumor has been 19.8 +/- 14.8 months in T2 tumors, and 22.67 +/- 19.72 months in T3 tumors (P > 0.05). There was very significant difference in recurrent rate between grade I and grade II, III patients (0 and 66.7%, P < 0.001).. CPD4-PDT is a safe and effective measure to prevent the recurrence in infiltrative bladder cancer after operation.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Transitional Cell; Chlorophyll; Female; Humans; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Photochemotherapy; Photosensitizing Agents; Postoperative Period; Prospective Studies; Urinary Bladder Neoplasms

Pheophorbide a is a photocytotoxic agent. To develop a tissue-specific, intracellularly targeted photoactive system, pheophorbide a was incorporated into immunoliposomes coated with a monoclonal antibody (T-43) directed against the T-24 bladder tumor cell line. The efficacy of this system was studied in vitro using the human bladder tumor cell line MGH-U1. Uptake and localization were determined by the fluorescence of the immunoliposome markers within biochemically resolved subcellular components. The results demonstrate localization of the immunoliposome markers within the lysosomes of the tumor cells. Specific monoclonal antibody enhancement of the immunoliposomes uptake by MGH-U1 cells was demonstrated by the use of soluble T-43 monoclonal antibody as a competitive inhibitor. Pheophorbide-a-loaded immunoliposomes were shown to be photocytotoxic towards MGH-U1 cells at concentrations equivalent to photosensitizer at 500 ng ml-1. Treated cells, when protected from light, showed no cytotoxicity. These results demonstrate that uptake of pheophorbide-a-containing immunoliposomes by target cells and subsequent delivery to the lysosomes cause photoactivated killing of tumor cells. The utilization of immunoliposomes for intracellular lysosomal targeting of photoactive drugs to tumor cells constitutes a potentially valuable approach to photodynamic therapeutics.

Topics: Antibodies, Monoclonal; Carcinoma, Transitional Cell; Cell Line; Cell Survival; Chlorophyll; Darkness; Drug Carriers; Humans; Light; Liposomes; Lysosomes; Radiation-Sensitizing Agents; Tumor Cells, Cultured; Urinary Bladder Neoplasms

We propose the use of acetoxymethyl esters of pH-sensitive amphipathic photosensitizers (PS) for photodynamic therapy (PDT). These compounds may be applicable for PDT involving endocytosis of lipophilic carriers leading to lysosomal uptake of the esterified PS by target cells. Partial and/or total enzymatic de-esterification may result in the extralysosomal distribution of the photoactive agents, possibly culminating in a multisite photochemical response. We report here the synthesis and properties of chlorin e6 triacetoxymethyl ester (CAME) and pheophorbide a acetoxymethyl ester (PAME). Chlorin e6 and pheophorbide a are photocytotoxic chlorins that possess free carboxylate groups and exhibit optimum wavelengths of excitation substantially red shifted relative to hematoporphyrin derivative. Acetoxymethyl esterification of chlorin e6 and pheophorbide a was accomplished with bromomethyl acetate. High-performance liquid chromatography allowed for the purification of PAME, in 87% purity, and CAME, in 63% yield and 94% purity, as well as the detection of the presumed mono- and diesters of chlorin e6 as transient intermediates in the synthesis of CAME. The ultraviolet-visible absorption, fluorescence excitation and emission, NMR and mass spectra of the chlorin e6 triester are consistent with those expected for CAME. The pH-sensitive amphipathicity of pheophorbide a and chlorin e6 but not CAME was demonstrated using a water/1-octanol partition assay. The production of pheophorbide a from PAME and the sequential formation of the di- and monoesters and free chlorin e6 from CAME, by the action of lysosomal esterases obtained from cancer cells, demonstrate the potential of cellular enzymes to convert the lipophilic esters to pH-sensitive amphipathic PS.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Carcinoma; Chlorophyll; Chlorophyllides; Esterases; Esterification; Esters; Humans; Hydrogen-Ion Concentration; Lysosomes; Photosensitizing Agents; Porphyrins; Solubility; Spectrometry, Fluorescence; Spectrophotometry; Urinary Bladder Neoplasms

Topics: Chlorophyll; Contrast Media; Female; Genital Neoplasms, Female; Humans; Iodized Oil; Lymphatic Metastasis; Lymphography; Male; Middle Aged; Staining and Labeling; Urinary Bladder Neoplasms