A Closer Look at Dark Toxicity of the Photosensitizer <scp>TMP</scp>yP in Bacteria

Eckl, Daniel Bernhard; Dengler, Linda; Nemmert, Marina; Eichner, Anja; Bäumler, Wolfgang; Huber, Harald

doi:10.1111/php.12846

Cited by 26 publications

(20 citation statements)

References 49 publications

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“…In this context, it is worth mentioning a recent report in which 5 μM of photosensitizer (TMPyP) was sufficient to produce aPDI using ambient lighting at a power density of 0.13 mW/cm 2 , within a 10-minute exposure time. 42…”

Section: Resultsmentioning

confidence: 99%

Rapid Uptake and Photodynamic Inactivation of Staphylococci by Ga(III)-Protoporphyrin IX

et al. 2018

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Antimicrobial photodynamic therapy (aPDT) is a promising method for the topical treatment of drug-resistant staphylococcal infections and can be further improved by identifying mechanisms that increase the specificity of photosensitizer uptake by bacteria. Here we show that Ga(III)-protoporphyrin IX chloride (Ga-PpIX), a fluorescent hemin analog with previously undisclosed photosensitizing properties, can be taken up within seconds by Staphylococcus aureus including multidrug-resistant strains such as MRSA. The uptake of Ga-PpIX by staphylococci is likely diffusion-limited and is attributed to the expression of high-affinity cell-surface hemin receptors (CSHRs), namely iron-regulated surface determinant (Isd) proteins. A structure-activity study reveals the ionic character of both the heme center and propionyl groups to be important for uptake specificity. Ga-PpIX was evaluated as a photosensitizer against S. aureus and several clinical isolates of MRSA using a visible light source, with antimicrobial activity at 0.03 μM with 10 s of irradiation by a 405 nm diode array (1.4 J/cm); antimicrobial activity could also be achieved within minutes using a compact fluorescent lightbulb. GaPpIX was not only many times more potent than PpIX, a standard photosensitizer featured in clinical aPDI, but also demonstrated low cytotoxicity against HEK293 cells and human keratinocytes. Ga-PpIX uptake was screened against a diverse panel of bacterial pathogens using a fluorescence-based imaging assay, which revealed rapid uptake by several Gram-positive species known to express CSHRs, suggesting future candidates for targeted aPDT.

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Section: Resultsmentioning

confidence: 99%

Rapid Uptake and Photodynamic Inactivation of Staphylococci by Ga(III)-Protoporphyrin IX

et al. 2018

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“…Some studies affirm that a pre-incubation period improves aPDT outcomes, and available data show periods on the order of minutes, mainly 5-15 min [12,124,125]. Dark toxicity depends on PS concentration and microorganisms experimental type (i.e., biofilms or planktonic cells) [122]. Note that a greater ratio of light/dark toxicity means a more advantageous PS [126].…”

Section: Incubation Periodmentioning

confidence: 97%

“…PSs' dark incubation period (IP), also called the pre-irradiation period, is an essential factor in promoting the contact between the microorganism cells and the PS. At present, aPDT assays must consider longer incubation times designated as dark control in order to recognize PS cytotoxicity in total absence of light [122]. The period between PS administration and shining the light named as pre-incubation time (PIT) for antimicrobial purposes should be small (few minutes) since the PS uptake by the bacteria is fast in contrast to eukaryotic cells (IP: 4-24 h) [123].…”

Section: Incubation Periodmentioning

confidence: 99%

An Insight into Advanced Approaches for Photosensitizer Optimization in Endodontics—A Critical Review

Diogo

Faustino

Neves

et al. 2019

JFB

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Apical periodontitis is a biofilm-mediated disease; therefore, an antimicrobial approach is essential to cure or prevent its development. In the quest for efficient strategies to achieve this objective, antimicrobial photodynamic therapy (aPDT) has emerged as an alternative to classical endodontic irrigation solutions and antibiotics. The aim of the present critical review is to summarize the available evidence on photosensitizers (PSs) which has been confirmed in numerous studies from diverse areas combined with several antimicrobial strategies, as well as emerging options in order to optimize their properties and effects that might be translational and useful in the near future in basic endodontic research. Published data notably support the need for continuing the search for an ideal endodontic photosensitizer, that is, one which acts as an excellent antimicrobial agent without causing toxicity to the human host cells or presenting the risk of tooth discoloration. The current literature on experimental studies mainly relies on assessment of mixed disinfection protocols, combining approaches which are already available with aPDT as an adjunct therapy. In this review, several approaches concerning aPDT efficiency are appraised, such as the use of bacteriophages, biopolymers, drug and light delivery systems, efflux pump inhibitors, negative pressure systems, and peptides. The authors also analyzed their combination with other approaches for aPDT improvement, such as sonodynamic therapy. All of the aforementioned techniques have already been tested, and we highlight the biological challenges of each formulation, predicting that the collected information may encourage the development of other effective photoactive materials, in addition to being useful in endodontic basic research. Moreover, special attention is dedicated to studies on detailed conditions, aPDT features with a focus on PS enhancer strategies, and the respective final antimicrobial outcomes. From all the mentioned approaches, the two which are most widely discussed and which show the most promising outcomes for endodontic purposes are drug delivery systems (with strong development in nanoparticles) and PS solubilizers.

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“…It has been reported that PS can reach and destroy blood cells, even when not administered intravenously [17,18]. That, in combination with residual dark toxicity of photosensitizers [19] can be a source of serious off target effects. To overcome these problems, novel delivery strategies have been developed.…”

Section: Introductionmentioning

confidence: 99%

Photoactive Pore Matrix for In Situ Delivery of a Photosensitizer in Vascular Smooth Muscle Cells Selective PDT

et al. 2019

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In this study we present the porous silica-based material that can be used for in situ drug delivery, offering effective supply of active compounds regardless its water solubility. To demonstrate usability of this new material, three silica-based materials with different pore size distribution as a matrix for doping with Photolon (Ph) and Protoporphyrin IX (PPIX) photosensitizers, were prepared. These matrices can be used for coating cardiovascular stents used for treatment of the coronary artery disease and enable intravascular photodynamic therapy (PDT), which can modulate the vascular response to injury caused by stent implantation—procedure that should be thought as an alternative for drug eluting stent. The FTIR spectroscopic analysis confirmed that all studied matrices have been successfully functionalized with the target photosensitizers. Atomic force microscopy revealed that resulting photoactive matrices were very smooth, which can limit the implantation damage and reduce the risk of restenosis. No viability loss of human peripheral blood lymphocytes and no erythrocyte hemolysis upon prolonged incubations on matrices indicated good biocompatibility of designed materials. The suitability of photoactive surfaces for PDT was tested in two cell lines relevant to stent implantation: vascular endothelial cells (HUVECs) and vascular smooth muscle cells (VSMC). It was demonstrated that 2 h incubation on the silica matrices was sufficient for uptake of the encapsulated photosensitizers. Moreover, the amount of the absorbed photosensitizer was sufficient for induction of a phototoxic reaction as shown by a rise of the reactive oxygen species in photosensitized VSMC. On the other hand, limited reactive oxygen species (ROS) induction in HUVECs in our experimental set up suggests that the proposed method of PDT may be less harmful for the endothelial cells and may decrease a risk of the restenosis. Presented data clearly demonstrate that porous silica-based matrices are capable of in situ delivery of photosensitizer for PDT of VSMC.

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A Closer Look at Dark Toxicity of the Photosensitizer TMPyP in Bacteria

Cited by 26 publications

References 49 publications

Rapid Uptake and Photodynamic Inactivation of Staphylococci by Ga(III)-Protoporphyrin IX

Rapid Uptake and Photodynamic Inactivation of Staphylococci by Ga(III)-Protoporphyrin IX

An Insight into Advanced Approaches for Photosensitizer Optimization in Endodontics—A Critical Review

Photoactive Pore Matrix for In Situ Delivery of a Photosensitizer in Vascular Smooth Muscle Cells Selective PDT

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