Novel Water-soluble Bacteriochlorophyll Derivatives for Vascular-targeted Photodynamic Therapy: Synthesis, Solubility, Phototoxicity and the Effect of Serum Proteins

Authors

  • Alexander Brandis,

    1. Department of Plant Sciences, The Weizmann Institute of Science, Rehovot, Israel
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  • Ohad Mazor,

    1. Department of Plant Sciences, The Weizmann Institute of Science, Rehovot, Israel
    2. Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel
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  • Eran Neumark,

    1. Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel
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  • Varda Rosenbach-Belkin,

    1. Department of Plant Sciences, The Weizmann Institute of Science, Rehovot, Israel
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  • Yoram Salomon,

    1. Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel
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  • Avigdor Scherz

    Corresponding author
    1. Department of Plant Sciences, The Weizmann Institute of Science, Rehovot, Israel
      *To whom correspondence should be addressed: Prof. Avigdor Scherz, Dept. of Plant Sciences, Weizmann Institute of Science, Rehovot 76100 Israel. Fax: 972–8-9344181; e-mail: avigdor.scherz@weizmann.ac.il
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  • Posted on the website on 19 April 2005

*To whom correspondence should be addressed: Prof. Avigdor Scherz, Dept. of Plant Sciences, Weizmann Institute of Science, Rehovot 76100 Israel. Fax: 972–8-9344181; e-mail: avigdor.scherz@weizmann.ac.il

ABSTRACT

New negatively charged water-soluble bacteriochlorophyll (Bchl) derivatives were developed in our laboratory for vascular-targeted photodynamic therapy (VTP). Here we focused on the synthesis, characterization and interaction of the new candidates with serum proteins and particularly on the effect of serum albumin on the photocytotoxicity of WST11, a representative compound of the new derivatives. Using several approaches, we found that aminolysis of the isocyclic ring with negatively charged residues markedly increases the hydrophilicity of the Bchl sensitizers, decreases their self-association constant and selectively increases their affinity to serum albumin, compared with other serum proteins. The photocytotoxicity of the new candidates in endothelial cell culture largely depends on the concentration of the serum albumin. Importantly, after incubation with physiological concentrations of serum albumin (500–600 μM), WST11 was found to be poorly photocytotoxic (>80% endothelial cell survival in cell cultures). However, in a recent publication (Mazor, O. et al. [2005] Photochem. Photobiol. 81, 342–351) we showed that VTP of M2R melanoma xenografts with a similar WST11 concentration resulted in ∼100% tumor flattening and >70% cure rate. We therefore propose that the two studies collectively suggest that the antitumor activity of WST11 and probably of other similar candidates does not depend on direct photointoxication of individual endothelial cells but on the vascular tissue response to the VTP insult.

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