Endosome Targeting meso-Tetraphenylchlorin-Chitosan Nanoconjugates for Photochemical Internalization

Biomacromolecules. 2017 Apr 10;18(4):1108-1126. doi: 10.1021/acs.biomac.6b01670. Epub 2017 Mar 15.


Four amphiphilic covalently linked meso-tetraphenylchlorin-chitosan nanoconjugates were synthesized and evaluated for use in photochemical internalization (PCI) in vitro and in vivo. The synthetic protocol for the preparation of two different hydrophobic chlorin photosensitizers, 5-(4-aminophenyl)-10,15,20-triphenylchlorin and 5-(4-carboxyphenyl)-10,15,20-triphenylchlorin, was optimized. These monofunctional photosensitizers were covalently attached to carrier chitosan via silyl-protected 3,6-di-O-tert-butyldimethylsilyl-chitosan (Di-TBDMS-chitosan) with 0.10 degree of substitution per glucosamine (DS). Hydrophilic moieties such as trimethylamine and/or 1-methylpiperazine were incorporated with 0.9 DS to give fully water-soluble conjugates after removal of the TBDMS groups. A dynamic light scattering (DLS) study confirmed the formation of nanoparticles with a 140-200 nm diameter. These nanoconjugates could be activated at 650 nm (red region) light, with a fluorescence quantum yield (ΦF) of 0.43-0.45, and are thus suitable candidates for use in PCI. These nanoconjugates were taken up and localized in the endocytic vesicles of HCT116/LUC human colon carcinoma cells, and upon illumination they substantially enhanced plasmid DNA transfection. The nanoconjugates were also evaluated in preliminary in vivo experiments in tumor-bearing mice, showing that the nanoconjugates could induce a strong photodynamic therapy (PDT) and also PCI effects in treatment with bleomycin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bleomycin
  • Chitosan / chemistry*
  • Endosomes / drug effects*
  • Female
  • HCT116 Cells
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Magnetic Resonance Spectroscopy
  • Mice
  • Mice, Nude
  • Nanoconjugates / chemistry*
  • Photochemistry
  • Photosensitizing Agents / chemistry*
  • Piperazines / chemistry
  • Polymers / chemistry
  • Porphyrins / chemistry
  • Spectroscopy, Fourier Transform Infrared
  • Transfection
  • Transport Vesicles / drug effects
  • Transport Vesicles / metabolism
  • Xenograft Model Antitumor Assays


  • 5-(4-carboxyphenyl)-10,15,20-triphenylchlorin
  • Nanoconjugates
  • Photosensitizing Agents
  • Piperazines
  • Polymers
  • Porphyrins
  • Bleomycin
  • Chitosan
  • 1-methylpiperazine