Photosensitisers – the progression from photodynamic therapy to anti-infective surfaces

Craig, Rebecca; McCoy, Colin; Gorman, Seán; Jones, David S.

doi:10.1517/17425247.2015.962512

Cited by 43 publications

(25 citation statements)

References 166 publications

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“…Thet herapeutic interest in Bax-mediated apoptosis encompasses aw ide array of diseases,f rom cancer to neuropathologies.A saconsequence,av ariety of tools have been developed to explore and/or perturb apoptotic pathways, including small molecule inhibitors and activators. [22] Light has been used, in conjunction with photosensitizers [23] or genetically expressed proteins, [24] to induce reactive oxygen species and cell death. Furthermore,avariety of lightresponsive small molecules have been described that trigger cell death via an array of miscellaneous mechanisms.…”

Section: Methodsmentioning

confidence: 99%

Optogenetic Apoptosis: Light‐Triggered Cell Death

et al. 2015

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An optogenetic Bax has been designed that facilitates light-induced apoptosis. We demonstrate that mitochondrial recruitment of a genetically encoded light-responsive Bax results in the release of mitochondrial proteins, downstream caspase 3 cleavage, changes in cellular morphology, and ultimately cell death. Mutagenesis of a key phosphorylatable residue or modification of the C-terminus mitigates background levels (dark) of apoptosis due to Bax overexpression. The mechanism of optogenetic Bax-mediated apoptosis was explored using a series of small molecules known to interfere with various steps in programmed cell death. Optogenetic Bax appears to form a mitochondrial apoptosis-induced channel analogous to that of endogenous Bax.

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Section: Methodsmentioning

confidence: 99%

Optogenetic Apoptosis: Light‐Triggered Cell Death

et al. 2015

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“…For instance, the PPIX precursor, 5-aminolevulinic acid (ALA), has been successfully used in the topical treatment of skin cancer and other dermatologic lesions (20,44,45). On the other hand, although PDT was first proposed as a means to kill microorganisms, only with the emergence of multidrug-resistant microorganisms has the use of PDT against microbes been revisited (20,46). Since then, several attempts to discover photosensitizing drugs suitable for antimicrobial and antiviral therapies have been made.…”

Section: Vesicular Stomatitis Virus Inactivation By Porphyrins Antimimentioning

confidence: 99%

Mechanisms of Vesicular Stomatitis Virus Inactivation by Protoporphyrin IX, Zinc-Protoporphyrin IX, and Mesoporphyrin IX

Cruz-Oliveira

Almeida

Freire

et al. 2017

Antimicrob Agents Chemother

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Virus resistance to antiviral therapies is an increasing concern that makes the development of broad-spectrum antiviral drugs urgent. Targeting of the viral envelope, a component shared by a large number of viruses, emerges as a promising strategy to overcome this problem. Natural and synthetic porphyrins are good candidates for antiviral development due to their relative hydrophobicity and pro-oxidant character. In the present work, we characterized the antiviral activities of protoprophyrin IX (PPIX), Znprotoporphyrin IX (ZnPPIX), and mesoporphyrin IX (MPIX) against vesicular stomatitis virus (VSV) and evaluated the mechanisms involved in this activity. Treatment of VSV with PPIX, ZnPPIX, and MPIX promoted dose-dependent virus inactivation, which was potentiated by porphyrin photoactivation. All three porphyrins inserted into lipid vesicles and disturbed the viral membrane organization. In addition, the porphyrins also affected viral proteins, inducing VSV glycoprotein cross-linking, which was enhanced by porphyrin photoactivation. Virus incubation with sodium azide and ␣-tocopherol partially protected VSV from inactivation by porphyrins, suggesting that singlet oxygen ( 1 O 2 ) was the main reactive oxygen species produced by photoactivation of these molecules. Furthermore, 1 O 2 was detected by 9,10-dimethylanthracene oxidation in photoactivated porphyrin samples, reinforcing this hypothesis. These results reveal the potential therapeutic application of PPIX, ZnPPIX, and MPIX as good models for broad antiviral drug design.KEYWORDS photoactivation, porphyrin, singlet oxygen, vesicular stomatitis virus, viral inactivation D espite the increasing number of antiviral drugs available nowadays, therapeutics for viral diseases often fail due to drug resistance development by the target viruses. In the search for antiviral agents with a broad spectrum of activity against viruses, antiviral agents targeting the viral envelope, a component shared by a large number of viruses, emerge as promising compounds able to overcome the drug resistance problem. Porphyrins, amphipathic molecules able to interact with membranes, appear to be good candidates for the development of such antivirals. Porphyrins are formed by four pyrrole rings linked by methine bonds. The nitrogen atoms in the center of the ring form a pocket able to coordinate metallic ions, conferring to porphyrin the ability to absorb light at additional wavelengths and act in catalytic transformations (1). These activities allow porphyrins to be involved in important biological processes, such as respiration (heme) and photosynthesis (chlorophyll and bacteriochlorophyll) (2).

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“…There are documents from ∼1200–2000 BC showing that Egyptian and Chinese physicians as well as Indian Hindu Ayurvedic practitioners used combinations of plant extracts with exposure to sunlight to treat skin disorders (Pathak and Fitzpatrick, 1992; Craig et al, 2014). For example, the Egyptians used the application of an extract of Ammi majus , a furanocoumarin-containing plant, associated with sun exposure to topically treat vitiligo.…”

Section: Brief History Of Photodynamic Therapymentioning

confidence: 99%

Antimicrobial photodynamic therapy: an effective alternative approach to control fungal infections

et al. 2015

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Skin mycoses are caused mainly by dermatophytes, which are fungal species that primarily infect areas rich in keratin such as hair, nails, and skin. Significantly, there are increasing rates of antimicrobial resistance among dermatophytes, especially for Trichophyton rubrum, the most frequent etiologic agent worldwide. Hence, investigators have been developing new therapeutic approaches, including photodynamic treatment. Photodynamic therapy (PDT) utilizes a photosensitive substance activated by a light source of a specific wavelength. The photoactivation induces cascades of photochemicals and photobiological events that cause irreversible changes in the exposed cells. Although photodynamic approaches are well established experimentally for the treatment of certain cutaneous infections, there is limited information about its mechanism of action for specific pathogens as well as the risks to healthy tissues. In this work, we have conducted a comprehensive review of the current knowledge of PDT as it specifically applies to fungal diseases. The data to date suggests that photodynamic treatment approaches hold great promise for combating certain fungal pathogens, particularly dermatophytes.

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Photosensitisers – the progression from photodynamic therapy to anti-infective surfaces

Cited by 43 publications

References 166 publications

Optogenetic Apoptosis: Light‐Triggered Cell Death

Optogenetic Apoptosis: Light‐Triggered Cell Death

Mechanisms of Vesicular Stomatitis Virus Inactivation by Protoporphyrin IX, Zinc-Protoporphyrin IX, and Mesoporphyrin IX

Antimicrobial photodynamic therapy: an effective alternative approach to control fungal infections

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