Phenazines and Photoactive Formulations: Promising Photodrugs for Photodynamic Therapy

Abstract

Photodynamic Therapy (PDT) is a therapeutic modality that can be applied with many photosensitizing compounds (PS). Photosensitization has shown promising results in damage against abnormal cell growth as cancer and inactivating a broad spectrum of microorganisms with no reported microbial resistance. Photodynamic processes occur by the light action at the appropriate wavelength in the presence of a PS that will be excited by the energy absorbed from the light source, where the interaction with the oxygen present in the cell will generate reactive oxygen species (ROS). The potential of phenazines as a photosensitizer is reviewed in this chapter as a practical guide to the future development of formulations that are effective for cancer treatment and microorganism control. Here we mainly summarize articles about phenazines from 2005 to 2021 when we performed a systematic search in the Science Direct, PubMed, Google Scholar, Web of Science, and Scopus databases. The carrier systems formed by micellar copolymers type Pluronic® have demonstrated effectiveness in incorporating several PS, ensuring its monomeric form for PDT applications. The fundamentals of the photosensitization mechanism are discussed. Studies have shown the beneficial impact of an appropriate incorporation technique to enhance the cellular uptake of phenazines compounds.

The dermacozines and light: a novel phenazine semiquinone radical based photocatalytic system from the deepest oceanic trench of the Earth

“…42 None of these compounds were prepared as stable radicals with illumination prior to being tested against pathogens/cancer cell lines. [40][41][42] The activity of dermacozines based on their water oxidising redox potentials in our work might be augmented with light, where their radicals may become more potent anticancer agents in nature.…”

“…The existing DFT computational chemistry reports predict large non-linear optical susceptibilities upon laser excitation, where all dermacozines showed high values at 800 nm, and particularly the dermacozine E, F, G-like structures displayed very large hyperpolarizabilities at 1064 nm. 34 Although at the mesmerizing depth of deep oceans visible photons reportedly exist from sources like the β − emitting 40 K decay to the 40 Ca stable isotope, bioluminescence, chemiluminescence, black smokers, and seismic light, 35,36 significant participation of light in the biological function of dermacozines due to the published low abundance of these photons is unlikely. Even if it was possible for the organism to make oxidising dermacozine radicals with light at that depth, this process will likely not participate in biomass formation in the hadal zone due to the same considerations.…”

“…5,38,39 Photosensitisation and photo-dynamic-Therapy (PDT) acting through generating ROS is a promising technique utilised in the treatment of cancer, viral-, bacterial-, and fungal infections, cardiovascular diseases, and dermatological conditions, with e.g., no reported antimicrobial resistance so far mentioned in the literature. 40 Incorporating photosensitised substances into nanostructures (e.g., copolymeric micelles, liposomal vesicles, nanosuspensions etc.) provides protection against biological breakdown, improves bio-transport and due to amplified bioavailability potentiates action at the site of action.…”

“…41,42 Most antibacterial and anticancer studies related to phenazines were reported in darkness. 40 There are only a few phenazines which were reported to be PDT active following visible light illumination, e.g., white light illuminated (Hg lamp) safranin O and Au nanoparticles incorporated into copolymer emulsion paint caused more lethal photosensitisation of Escherichia coli and Staphylococcus aureus, and possessed less toxic effect under dark conditions. 41 In another study neutral red delivered with thioglycolate covered Au nanoparticles and illuminated with a λ = 440 nm Twin Flex LASER LED MMoptics system led to reduced cell viability of NIH-3T3 fibroblast and 4T1 tumour cell lines.…”