Tetraphenylporphyrin tethered chitosan based carriers for photochemical transfection

J Med Chem. 2013 Feb 14;56(3):807-19. doi: 10.1021/jm301270r. Epub 2013 Jan 28.

Abstract

Water-soluble amphiphilic chitosan nanocarriers tethered with the photosensitizer meso-tetraphenylporphyrin were synthesized in a seven-step procedure, starting from 3,6-di-O-tert-butyldimethylsilyl-chitosan and 5-(p-aminophenyl)-10,15,20-triphenylporphyrin. The lipophilic photosensitizer could be introduced in a quantitative and reproducible reaction to give either 0.1 or 0.25 degrees of substitution per glucosamine monomer. Fluorescence and NMR investigations revealed the dynamic structures of the carriers, which formed nanoparticles in aqueous solution with a core of π-stacked photosensitizers. These carriers can then unfold in the lipophilic environment, and the photosensitizer moiety can thus be inserted into the cell membrane. The efficacy of the carriers for photochemical internalization (PCI) mediated gene delivery was evaluated in vitro using the HCT116/LUC human colon carcinoma cell line. The efficacy of transfection was comparable to what could be achieved by the reference compound and current clinical candidate TPCS(2a).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chitosan / chemistry*
  • Magnetic Resonance Spectroscopy
  • Microscopy, Electron, Scanning
  • Photochemical Processes
  • Porphyrins / chemistry*

Substances

  • Porphyrins
  • tetraphenylporphyrin
  • Chitosan