In Vitro Photodynamic Activity of a Series of Methylene Blue Analogues¶

The effect of divalent cations (calcium and magnesium) and a permeabilizing agent (EDTA) on the uptake of a cationic photosensitizer (PS), methylene blue (MB), and two anionic PSs, rose bengal (RB) and indocyanine green (ICG), by Gram-positive Enterococcus faecalis and Gram-negative Actinobacillus actinomycetemcomitans was examined. The possible roles of multidrug efflux pumps and protein transporters in photosensitizer uptake were assessed in E. faecalis cells by studies using an efflux pump inhibitor (verapamil) and trypsin treatment respectively. Divalent cations enhanced the uptake and photodynamic inactivation potential of both RB and ICG in E. faecalis and A. actinomycetemcomitans, while they decreased the uptake and bacterial killing by MB. Verapamil increased the uptake of RB (possibly due to efflux pump inhibition), whereas trypsin treatment resulted in significant decrease in RB and ICG uptake. The results suggested that the uptake of anionic PSs by bacterial cells may be mediated through a combination of electrostatic charge interaction and by protein transporters, while the uptake of cationic PSs, as previously reported, is mediated by electrostatic interactions and self promoted uptake pathways.

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“…MB is a positively-charged, hydrophilic phenothiazinium PS with an absorbance maximum of 664 nm23 (Fig. 1).…”

Section: Discussionmentioning

confidence: 99%

Uptake pathways of anionic and cationic photosensitizers into bacteria

George

Hamblin

Kishen

2009

Photochem Photobiol Sci

217

141

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“…Electron delocalization in MB results in a partial positive charge being located on both nitrogen and sulfur atoms, which may increase the permeability of MB through membranes. Thus, MBH 2 and MB can enter the mitochondria [53] and other intracellular compartments such as lysosomes [54]. MB is the most effective agent reported so far to delay cellular senescence and enhance specific biochemical activities of the mitochondria.…”

Section: Redox Active Agentsmentioning

confidence: 99%

Mitochondrial pharmacology: Electron transport chain bypass as strategies to treat mitochondrial dysfunction

2012

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Mitochondrial dysfunction (primary or secondary) is detrimental to intermediary metabolism. Therapeutic strategies to treat/prevent mitochondrial dysfunction could be valuable for managing metabolic and age-related disorders. Here, we review strategies proposed to treat mitochondrial impairment. We then concentrate on redox-active agents, with mild-redox potential, who shuttle electrons among specific cytosolic or mitochondrial redox-centers. We propose that specific redox agents with mild redox potential (−0.1 V; 0.1 V) improve mitochondrial function because they can readily donate or accept electrons in biological systems, thus they enhance metabolic activity and prevent reactive oxygen species (ROS) production. These agents are likely to lack toxic effects because they lack the risk of inhibiting electron transfer in redox centers. This is different from redox agents with strong negative (−0.4 V; −0.2 V) or positive (0.2 V; 0.4 V) redox potentials who alter the redox status of redox-centers (i.e., become permanently reduced or oxidized). This view has been demonstrated by testing the effect of several redox active agents on cellular senescence. Methylene blue (MB, redox potential ≅10 mV) appears to readily cycle between the oxidized and reduced forms using specific mitochondrial and cytosolic redox centers. MB is most effective in delaying cell senescence and enhancing mitochondrial function in vivo and in vitro. Mild-redox agents can alter the biochemical activity of specific mitochondrial components, which then in response alters the expression of nuclear and mitochondrial genes. We present the concept of mitochondrial electron-carrier bypass as a potential result of mild-redox agents, a method to prevent ROS production, improve mitochondrial function, and delay cellular aging. Thus, mild-redox agents may prevent/delay mitochondria-driven disorders.

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“…[58,59] PSs that localize to and destroy the endoplasmic reticulum [60] and Golgi apparatus [61,62] may also initiate cell-signaling cascades that result in cell death. [61] It should also be noted that cellular redistribution of PSs during therapy has been reported, [63,64] which would allow for the destruction of cellular organelles not originally involved in PS uptake.…”

Section: Photodynamic Therapy In Vitromentioning

confidence: 99%

Label‐Free, Longitudinal Visualization of PDT Response In Vitro with Optical Coherence Tomography

Jung

Nichols

Klein

et al. 2012

Israel Journal of Chemistry

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A major challenge in creating and optimizing therapeutics in the fight against cancer is visualizing and understanding the microscale spatiotemporal treatment response dynamics that occur in patients. This is especially true for photodynamic therapy (PDT), where therapeutic optimization relies on understanding the interplay between factors such as photosensitizer localization and uptake, in addition to light dose and delivery rate. In vitro 3D culture systems that recapitulate many of the biological features of human disease are powerful platforms for carrying out detailed studies on PDT response and resistance. Current techniques for visualizing these models, however, often lack accuracy due to the perturbative nature of the sample preparation, with light attenuation complicating the study of intact models. Optical coherence tomography (OCT) is an ideal method for the long-term, non-perturbative study of in vitro models and their response to PDT. Monitoring the response of 3D models to PDT by time-lapse OCT methods promises to provide new perspectives and open the way to cancer treatment methodologies that can be translated towards the clinic.

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In Vitro Photodynamic Activity of a Series of Methylene Blue Analogues¶

Cited by 142 publications

References 22 publications

Uptake pathways of anionic and cationic photosensitizers into bacteria

Uptake pathways of anionic and cationic photosensitizers into bacteria

Mitochondrial pharmacology: Electron transport chain bypass as strategies to treat mitochondrial dysfunction

Label‐Free, Longitudinal Visualization of PDT Response In Vitro with Optical Coherence Tomography

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