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In Vitro and In Vivo Photosensitization by Protoporphyrins Possessing Different Lipophilicities and Vertical Localization in the Membrane
Author(s) -
Bronshtein Irena,
Aulova Svetlana,
Juzeniene Asta,
Lanl Vladimir,
Ma LiWei,
Smith Kevin M.,
Malik Zvi,
Moan Johan,
Ehrenberg Benjamin
Publication year - 2006
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1562/2006-04-02-ra-865
Subject(s) - protoporphyrin ix , photodynamic therapy , chemistry , cytoplasm , in vitro , in vivo , lipophilicity , fluorescence microscope , biophysics , singlet oxygen , intracellular , photobleaching , fluorescence , membrane , tetrapyrrole , cell , biochemistry , biology , oxygen , physics , microbiology and biotechnology , organic chemistry , quantum mechanics , enzyme
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 (PPIX C6 ) by WiDR and CT26 cells was investigated by fluorescence microscopy and by fluorescence intensity from the cells. The uptake of PPIX C6 increased almost linearly with incubation length for over 24 h, whereas for PPIX only 1h 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 PPIX C6 followed by light exposure showed a significant delay in their growth.