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Diamino acid derivatives of PpIX as potential photosensitizers for photodynamic therapy of squamous cell carcinoma and prostate cancer: In vitro studies
Authors:Mateusz Kwitniewski  Asta Juzeniene  Li-Wei Ma  Renata Glosnicka  Alfreda Graczyk  Johan Moan
Affiliation:1. Department of Molecular Microbiology and Serology, National Salmonella Centre, Medical University of Gdansk, ul. Do Studzienki 38, 80-227 Gdansk, Poland;2. Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Rikshospitalet University Hospital, Montebello, 0310 Oslo, Norway;3. R&D Immunolab Company Ltd., ul. Al. Zwyci?stwa 96/98, 81-451 Gdynia, Poland;4. Institute of Optoelectronics, Military University of Technology, ul. Kaliskiego 2, 00-908 Warsaw, Poland;5. Institute of Physics, University of Oslo, Blindern, 0316 Oslo, Norway
Abstract:Photodynamic therapy (PDT) is an alternative treatment modality involving light activated drugs, called photosensitizers (PSs), to treat cancer and non-cancerous conditions. The search for new compounds which might become effective PSs is the major direction for PDT development. In the present work we have studied the dark toxicity, intracellular localization and photodynamic properties of four potential, water soluble, second generation PSs – PP(Arg)2, PP(Ser)2Arg2, PP(Ala)2Arg2, PP(Phe)2Arg2, all diamino acid derivatives of protoporphyrin IX. Human prostate cancer (DU-145) and squamous carcinoma (A431) cells were used as experimental model.Among investigated compounds PP(Ser)2Arg2 exhibited the lowest dark toxicity and the highest PDT effectiveness towards both cell lines. Fluorescence microscopy revealed the time-dependent changes in intracellular localization of the PS which were related to the phototoxicity. The results show that PP(Ser)2Arg2 may be a potential PS for PDT.
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