Cationic Triarylmethane Photosensitizers For Selective Photochemotherapy: Victoria Blue-Bo, Victoria Blue-R And Malachite Green

The conceptual basis for the development of mitochondrial targeting as a novel therapeutic strategy for both chemotherapy and photochemotherapy of neoplastic diseases rests on the observation that enhanced mitochondrial membrane potential is a common tumor cell phenotype. The potential of this strategy is highlighted by the fact that the toxic effects associated with a number of cationic dyes known to localize in energized cell mitochondria are much more pronounced in tumor cells than in normal cells. Here we evaluate the phototoxic properties of four bromine derivatives of rhodamine-123 toward human uterine sarcoma (MES-SA) and green monkey kidney (CV-1) cells and compare the degrees of tumor cell selectivity associated with these dyes with those associated with two model mitochondrial triarylmethanes (crystal violet and ethyl violet). Selective phototoxicity toward tumor cells was found to be highly dependent upon the lipophilic/hydrophilic character of the cationic photosensitizer. Our experimental data have indicated that the probability of success of mitochondrial targeting in (photo)chemotherapy of neoplastic diseases is higher when the octan-1-ol/water partition coefficient of the drug candidate falls within approximately two orders of magnitude from that of the prototypical mitochondria-specific dye rhodamine-123.

Section: Resultsmentioning

confidence: 84%

Photophysical, Photochemical, and Tumor‐selectivity Properties of Bromine Derivatives of Rhodamine‐123

Lacerda

Abraham

Stringfellow

et al. 2005

“…These cells demonstrate a high metabolism and are rich in mitochondria, which is important for photosensitivity to dyes accumulating in mitochondria (VB-BO). They are also rich in lipid components of cytoplasmic membranes, which is important for photosensitivity to dyes accumulating inside lipids (MC540) (4,6,14,24). The accumulation of photosensitizing dyes in cell membranes or mitochondria resulted in preferential killing of monocytes isolated as a pure population and also within PBMC.…”

Section: Discussionmentioning

confidence: 99%

“…It was shown that many of these dyes penetrate plasma and mitochondria1 membranes and can be concentrated up to 1000-fold in mitochondria (43). It was reported that a compound from this group, Victoria blue BO (VB-BO), a triarylmethane derivative, induced in vitro killing of human squamous (FaDu), colon (CX-1) carcinoma and human (NEL) and murine (B-16) melanoma cells (6). More recently, Fiedorowicz el al.…”

Section: Introductionmentioning

confidence: 99%

“…Victoria blue BO is accumulated in the cell mitochondria and after irradiation produces selective inhibition of the mitochondria1 respiratory complex 1 (4). A low intrinsic toxicity against both solid tumor cell lines and leukemic cells, very low concentrations of dye M) and the moderate light intensities needed to achieve a significant reduction in the percentage of living malignant cells make VB-BO a promising photosensitizer (6,7). However, no data regarding phototoxicity of VB-BO on normal mature blood cells have been described.…”

Section: Introductionmentioning

confidence: 99%

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The Photodynamic Effect of Victoria Blue BO on Peripheral Blood Mononuclear and Leukemic Cells

Fiedorowicz

Pituch‐Noworolska

Zembala

1997

The photodynamic effect of Victoria blue BO (VB-BO) and photoirradiation on peripheral blood mononuclear cells was studied. The cells were preincubated with VB-BO followed by photoirradiation and overnight culture. The highest percentage of dead cells (propidium iodide assay in flow cytometry) was seen in the monocyte population. The lymphocytes showed a lower sensitivity to VB-BO photodynamic action than the monocytes (12% vs 80% of PI-positive cells). The effect of VB-BO and phototreatment on lymphocyte function was studied using a mitogen-induced proliferation assay. A decrease of mitogen response was observed. The VB-BO and photoirradiation were also used on leukemic cells. The leukemic cells from acute myeloid leukemia and B precursors leukemia were sensitive to VB-BO photodynamic action. The high VB-BO sensitivity of monocytes and leukemic cells (myeloid and lymphoid B derived) suggests possible application of VB-BO for selective depletion of monocytes or sensitive leukemic cells.

“…So far, photothermal sensitization has been applied in biological systems by using endogenous chromophores such as melanin to achieve the fragmentation of melanosomes (6,7) and hemoglobin to induce the destruction of blood vessels and hemostasis (8)(9)(10). There are several dyes, such as metalloporphyrins or -phthalocyanines (1 l), triphenylmethane derivatives (12) and azo dyes (13) that exhibit intense absorption bands in the visible spectral range and are essentially nonluminescent and devoid of any detectable photochemical activity. These are potential exogenous photothermal sensitizers.…”

Section: Introductionmentioning

confidence: 99%

Irradiation of Amelanotic Melanoma Cells with 532 nm High Peak Power Pulsed Laser Radiation in the Presence of the Photothermal Sensitizer Cu(II)‐Hematoporphyrin: A New Approach to Cell Photoinactivation

Soncin

Busetti

Fusi

et al. 1999

Cu(II)-hematoporphyrin (CuHp) was efficiently accumulated by B78H1 amelanotic melanoma cells upon incubation with porphyrin concentrations up to 52 microM. When the cells incubated for 18 h with 13 microM CuHp were irradiated with 532 nm light from a Q-switched Nd: YAG laser operated in a pulsed mode (10 ns pulses, 10 Hz) a significant decrease in cell survival was observed. The cell photoinactivation was not the consequence of a photodynamic process, as CuHp gave no detectable triplet signal upon laser flash photolysis excitation and no decrease in cell survival was observed upon continuous wave irradiation. Thus, it is likely that CuHp sensitization takes place by photothermal pathways. The efficiency of the photoprocess was modulated by different parameters; thus, while varying the amount of added CuHp in the 3.25-26 microM range had little effect, pulse energies larger than 50 mJ and irradiation times of at least 120 s were necessary to induce a cell inactivation of about 50%. The porphyrin-cell incubation time prior to irradiation had a major influence on cell survival, suggesting that the nature of the CuHp microenvironment can control the efficiency of photothermal sensitization.