phytochlorin and Cholangiocarcinoma

New methods for the endoscopic selective ablation of locally advanced pancreaticobiliary malignancies as a minimally invasive approach are needed. Our aim was to examine the feasibility and safety of endoscopic ultrasonography (EUS)-guided photodynamic therapy (PDT) for local tumor control in patients with locally advanced pancreaticobiliary malignancies.. A chlorin e6 derivative and a flexible laser-light catheter were used to perform EUS-guided PDT in four patients with locally advanced pancreaticobiliary malignancies.. EUS-guided PDT was technically feasible in all four patients with locally advanced pancreaticobiliary malignancies (two in the caudate lobe of the liver, one in the far distal bile duct, and one in the tail of the pancreas). No treatment-related complications occurred. The median volume of necrosis produced by PDT was 4.0 cm(3) (range 0.7 - 11.3). Disease remained stable in all four patients during a median follow-up of 5 months (range 3 - 7).. These preliminary data suggest that EUS-guided PDT with a second-generation photosensitizer and a flexible laser probe is feasible and safe.

Topics: Aged; Bile Duct Neoplasms; Catheters; Chlorophyllides; Cholangiocarcinoma; Endosonography; Feasibility Studies; Follow-Up Studies; Humans; Male; Middle Aged; Pancreatic Neoplasms; Photochemotherapy; Photosensitizing Agents; Pilot Projects; Porphyrins; Treatment Outcome; Ultrasonography, Interventional

In this study, the effect of chlorin e6-based photodynamic therapy (Ce6-PDT) was investigated in human intrahepatic (HuCC-T1) and extrahepatic (SNU1196) cholangiocarcinoma (CCA) cells. The amount of intracellular Ce6 increased with increasing Ce6 concentration administered, or with incubation time, in both cell lines. The ability to take up Ce6 and generate reactive oxygen species after irradiation at 1.0 J/cm(2) did not significantly differ between the two CCA cell types. However, after irradiation, marked differences were observed for photodamage and apoptotic/necrotic signals. HuCC-T1 cells are more sensitive to Ce6-PDT than SNU1196 cells. Total glutathione (GSH) levels, glutathione peroxidase and glutathione reductase activities in SNU1196 cells were significantly higher than in HuCC-T1 cells. With inhibition of enzyme activity or addition of GSH, the phototoxic effect could be controlled in CCA cells. The intracellular level of GSH is the most important determining factor in the curative action of Ce6-PDT against tumor cells.

Topics: Apoptosis; Cell Survival; Cells, Cultured; Chlorophyllides; Cholangiocarcinoma; Dose-Response Relationship, Drug; Humans; Oxidative Stress; Photochemotherapy; Photosensitizing Agents; Porphyrins; Structure-Activity Relationship

Chitosan was hydrophobically modified with ursodeoxycholic acid (UDCA) to fabricate nano-photosensitizer for photodynamic therapy (PDT) of HuCC-T1 cholangiocarcinoma cells. Synthesis of UDCA-conjugated chitosan (ChitoUDCA) was confirmed using (1)H NMR spectra. Chlorin E6 (Ce6) was used as a photosensitizer and incorporated into ChitoUDCA nanoparticles through formation of ion complexes. Morphology of Ce6-incorporated ChitoUDCA nanoparticles was observed using TEM and their shapes were spherical with sizes around 200-400 nm. The PDT potential of Ce6-incorporated ChitoUDCA nanoparticles were studied with HuCC-T1 human cholangiocarcinoma cells. The results showed that ChitoUDCA nanoparticles enhances of Ce6 uptake into tumor cells, phototoxicity, and ROS generation compared to Ce6 itself. Furthermore, Ce6-incorporated ChitoUDCA nanoparticles showed quenching in aqueous solution and sensing at tumor cells. We suggest that Ce6-incorporated ChitoUDCA nanoparticles are promising candidates for PDT of cholangiocarcinoma cells.

Topics: Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biological Transport; Cell Line, Tumor; Chemistry, Pharmaceutical; Chitosan; Chlorophyllides; Cholangiocarcinoma; Drug Carriers; Humans; Magnetic Resonance Spectroscopy; Microscopy, Electron, Transmission; Particle Size; Photochemotherapy; Photosensitizing Agents; Porphyrins; Reactive Oxygen Species; Technology, Pharmaceutical; Ursodeoxycholic Acid