title: Endosome Targeting meso-Tetraphenylchlorin-Chitosan Nanoconjugates for Photochemical Internalization.
abstract: 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.
authors.affiliation: Faculty of Pharmaceutical Sciences, School of Health Sciences, University of Iceland , Hofsvallagata 53, IS-107 Reykjavik, Iceland.|PCI Biotech AS , Ullernchauséen 64, N0379 Oslo, Norway.
authors.forename: Vivek S
authors.initials: VS
authors.lastname: Gaware
authors.affiliation: PCI Biotech AS , Ullernchauséen 64, N0379 Oslo, Norway.|Oslo University Hospital , The Norwegian Radium Hospital, Institute for Cancer Research, Department of Radiation Biology, Montebello, N-0310 Oslo, Norway.
authors.forename: Monika
authors.initials: M
authors.lastname: Håkerud
authors.affiliation: Oslo University Hospital , The Norwegian Radium Hospital, Institute for Cancer Research, Department of Radiation Biology, Montebello, N-0310 Oslo, Norway.
authors.forename: Asta
authors.initials: A
authors.lastname: Juzeniene
authors.affiliation: PCI Biotech AS , Ullernchauséen 64, N0379 Oslo, Norway.
authors.forename: Anders
authors.initials: A
authors.lastname: Høgset
authors.affiliation: Oslo University Hospital , The Norwegian Radium Hospital, Institute for Cancer Research, Department of Radiation Biology, Montebello, N-0310 Oslo, Norway.
authors.forename: Kristian
authors.initials: K
authors.lastname: Berg
authors.affiliation: Faculty of Pharmaceutical Sciences, School of Health Sciences, University of Iceland , Hofsvallagata 53, IS-107 Reykjavik, Iceland.
authors.forename: Már
authors.identifier: 0000-0003-0363-3316
authors.initials: M
authors.lastname: Másson
mesh_terms: D000818:Animals; D001761:Bleomycin; D048271:Chitosan / Q000737:chemistry*; D011992:Endosomes / Q000187:drug effects*; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008819:Mice, Nude; D058726:Nanoconjugates / Q000737:chemistry*; D010777:Photochemistry; D017319:Photosensitizing Agents / Q000737:chemistry*; D010879:Piperazines / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011166:Porphyrins / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D014162:Transfection; D022161:Transport Vesicles / Q000187:drug effects / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: C513508:5-(4-carboxyphenyl)-10,15,20-triphenylchlorin; D058726:Nanoconjugates; D017319:Photosensitizing Agents; D010879:Piperazines; D011108:Polymers; D011166:Porphyrins; D001761:Bleomycin; D048271:Chitosan; C048073:1-methylpiperazine