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    Tetraphenylporphyrin Tethered Chitosan Based Carriers forPhotochemical Transfection

    Year: 2013

    Journal: Journal of Medicinal Chemistry, 56, pp 807-819, 20130926

    Authors: Vivek S. Gaware, Monika Håkerud, Kristján Leósson, Sigrídur Jónsdóttir, Anders Høgset,Kristian Berg, Már Másson

    Organizations: Faculty of Pharmaceutical Sciences, School of Health Sciences, University of Iceland, Hofsvallagata 53, IS-107 Reykjavík, IcelandPCI Biotech AS, N-1366 Lysaker, NorwayOslo University Hospital, The Norwegian Radium Hospital, Institute for Cancer Research, Department of Radiation Biology,N-0310 Oslo, Norway∥Department of Physics, Science Institute, University of Iceland, Dunhagi 3, IS-107 Reykjavik, Iceland⊥Department of Chemistry, Science Institute, University of Iceland, Dunhagi 3, IS-107 Reykjavik, Iceland

    Water-soluble amphiphilic chitosan nanocarrierstethered with the photosensitizer meso-tetraphenylporphyrinwere 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 photosensitizercould be introduced in a quantitative and reproducible reactionto give either 0.1 or 0.25 degrees of substitution perglucosamine monomer. Fluorescence and NMR investigationsrevealed the dynamic structures of the carriers, which formednanoparticles in aqueous solution with a core of π-stackedphotosensitizers. These carriers can then unfold in the lipophilic environment, and the photosensitizer moiety can thus beinserted into the cell membrane. The efficacy of the carriers for photochemical internalization (PCI) mediated gene delivery wasevaluated in vitro using the HCT116/LUC human colon carcinoma cell line. The efficacy of transfection was comparable to whatcould be achieved by the reference compound and current clinical candidate TPCS2a.