Effect of the lipophilic/hydrophilic character of cationic triarylmethane dyes on their selective phototoxicity toward tumor cells

Ik Kandela, W. Lee, Guilherme L. Indig*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    30 Scopus citations

    Abstract

    The observation that enhanced mitochondrial transmembrane potential is a prevalent tumor cell phenotype has provided the conceptual basis for the development of mitochondrial targeting as a novel therapeutic strategy for both chemo- and photochemotherapy of neoplastic diseases. Because the plasma transmembrane potential is negative on the inner side of the cell and the mitochondrial transmembrane potential is negative on the inner side of this organelle, extensively conjugated cationic molecules (dyes) displaying appropriate structural features are driven electrophoretically through these membranes and tend to accumulate inside energized mitochondria. As a result of the higher mitochondrial transmembrane potential typical of tumor cells, a number of cationic dyes preferentially accrue and are retained for longer periods in the mitochondria of these cells compared to normal cells. This differential in both drug loading and retention brings about the opportunity to attack and destroy tumor cells with a high degree of selectivity. Only a small subset of the cationic dyes known to accumulate in energized mitochondria mediate the destruction of tumor cells with a high degree of selectivity, and the lack of a reliable model to describe the structural determinants of this tumor specificity has prevented mitochondrial targeting from becoming a more reliable therapeutic strategy. We describe here a systematic study of how the molecular structure of closely related cationic triarylmethanes affects the selectivity with which these dyes mediate the photochemical destruction of tumor cells. Based on our observations of how the lipophilic/hydrophilic character of these dyes affects tumor selectivity, we propose a simple model to assist in the design of new drugs tailored specifically for imaging and selective destruction of neoplastic tissue via mitochondrial targeting.

    Original languageEnglish (US)
    Pages (from-to)157-169
    Number of pages13
    JournalBiotechnic and Histochemistry
    Volume78
    Issue number3-4
    DOIs
    StatePublished - Jun 1 2003

    Keywords

    • Crystal violet
    • Mitochondrial targeting
    • Mitochondrion
    • Partition coefficients
    • Photochemotherapy
    • Rhodamine-123
    • Triarylmethane dyes
    • Tumor cells
    • Tumor therapy

    ASJC Scopus subject areas

    • Histology
    • Medical Laboratory Technology

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