Ursodeoxycholic acid-conjugated chitosan for photodynamic treatment of HuCC-T1 human cholangiocarcinoma cells

Int J Pharm. 2013 Sep 15;454(1):74-81. doi: 10.1016/j.ijpharm.2013.06.035. Epub 2013 Jul 6.

Abstract

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.

Keywords: Chitosan; Chlorin e6; Cholangiocarcinoma; Photodynamic therapy; Ursodeoxycholic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bile Duct Neoplasms / metabolism
  • Bile Duct Neoplasms / pathology*
  • Bile Ducts, Intrahepatic / drug effects*
  • Bile Ducts, Intrahepatic / metabolism
  • Bile Ducts, Intrahepatic / pathology
  • Biological Transport
  • Cell Line, Tumor
  • Chemistry, Pharmaceutical
  • Chitosan / chemistry*
  • Chlorophyllides
  • Cholangiocarcinoma / metabolism
  • Cholangiocarcinoma / pathology*
  • Drug Carriers*
  • Humans
  • Magnetic Resonance Spectroscopy
  • Microscopy, Electron, Transmission
  • Particle Size
  • Photochemotherapy*
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology*
  • Porphyrins / chemistry
  • Porphyrins / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Technology, Pharmaceutical / methods
  • Ursodeoxycholic Acid / chemistry
  • Ursodeoxycholic Acid / metabolism*

Substances

  • Chlorophyllides
  • Drug Carriers
  • Photosensitizing Agents
  • Porphyrins
  • Reactive Oxygen Species
  • phytochlorin
  • Ursodeoxycholic Acid
  • Chitosan