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1 September 2006 In Vitro and In Vivo Photosensitization by Protoporphyrins Possessing Different Lipophilicities and Vertical Localization in the Membrane
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Abstract

Photodynamic therapy (PDT) is being evaluated in clinical trials for treatment of various oncologic and ophthalmic diseases. The main cause for cell inactivation and retardation of tumor growth after photoactivation of sensitizers is very short-lived singlet oxygen molecules that are produced and have limited diffusion distances. In this paper we show that the extent of biological damage can be modulated by using protoporphyrin, which was modified to increase its lipophilicity, and which also places the tetrapyrrole core deeper within the membrane by the carboxylate groups being anchored at the lipid:water interface. The uptake of the parent molecule (PPIX) and its diheptanoic acid analogue (PPIXC6) by WiDR and CT26 cells was investigated by fluorescence microscopy and by fluorescence intensity from the cells. The uptake of PPIXC6 increased almost linearly with incubation length for over 24 h, whereas for PPIX only 1 h was needed to reach maximal intracellular concentration. Fluorescence microscopy of both cell lines indicated that both drugs were distributed diffusely in the plasma membrane and cytoplasm, but remained outside the nucleus. The efficiency of in vitro inactivation of WiDr and CT26 cells increased with the length of the alkylcarboxylic chain. Tumors in mice that were treated with PPIX-PDT grew more slowly than control tumors. However, tumors that were given PPIXC6 followed by light exposure showed a significant delay in their growth.

Irena Bronshtein, Svetlana Aulova, Asta Juzeniene, Vladimir Iani, Li-Wei Ma, Kevin M. Smith, Zvi Malik, Johan Moan, and Benjamin Ehrenberg "In Vitro and In Vivo Photosensitization by Protoporphyrins Possessing Different Lipophilicities and Vertical Localization in the Membrane," Photochemistry and Photobiology 82(5), 1319-1325, (1 September 2006). https://doi.org/10.1562/2006-04-02-RA-865
Received: 2 April 2006; Accepted: 31 May 2006; Published: 1 September 2006
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