Photodynamic effect of lanthanide derivatives of meso-tetra(N-methyl-4-pyridyl)porphine against Staphylococcus aureus.

Jurczak, Agata; Szramka, Bozena; Grinholc, Mariusz; Legendziewicz, J.; Bielawski, Krzysztof Piotr

doi:10.18388/abp.2008_3064

Cited by 10 publications

(6 citation statements)

References 17 publications

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“…A better understanding of the biochemical and genetic mechanisms of S. aureus pathogenicity will lead to improved prevention and treatment strategies. Nevertheless, although various approaches are being considered, including special procedures of antibiotic treatment, photodynamic therapy or bacteriophage therapy (see, for example: Dzwonkowska et al, 2007;Grinholc et al, 2008;Jurczak et al, 2008;Mann, 2008;Grinholc et al 2008), it appears to be a formidable task.…”

Section: Discussionmentioning

confidence: 99%

Staphylococcus aureus as an infectious agent: overview of biochemistry and molecular genetics of its pathogenicity.

Plata

Rosato²,

Węgrzyn³

2009

Acta Biochim Pol

185

125

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Although it is estimated that 20-30% of the general human population are carriers of Staphylococcus aureus, this bacterium is one of the most important etiological agents responsible for healthcare-associated infections. The appearance of methicillin resistant S. aureus (MRSA) strains has created serious therapeutical problems. Detailed understanding of the mechanisms of S. aureus infections seems necessary to develop new effective therapies against this pathogen. In this article, we present an overview of the biochemical and genetic mechanisms of pathogenicity of S. aureus strains. Virulence factors, organization of the genome and regulation of expression of genes involved in virulence, and mechanisms leading to methicilin resistance are presented and briefly discussed.

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Section: Discussionmentioning

confidence: 99%

Staphylococcus aureus as an infectious agent: overview of biochemistry and molecular genetics of its pathogenicity.

Plata

Rosato²,

Węgrzyn³

2009

Acta Biochim Pol

185

125

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“…In our work we did not focused on examining the dependence of killing rate vs. light dose. We performed all photodynamic inactivation studies on one light dose (12 J/cm 2 ) chosen as optimal based on our previously published data concerning S. aureus photoinactivation as well as phototoxicity assays performed on dermal human fibroblasts [ 46 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

Superoxide dismutase is upregulated in Staphylococcus aureus following protoporphyrin-mediated photodynamic inactivation and does not directly influence the response to photodynamic treatment

et al. 2010

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BackgroundStaphylococcus aureus, a major human pathogen causes a wide range of disease syndromes. The most dangerous are methicillin-resistant S. aureus (MRSA) strains, resistant not only to all β-lactam antibiotics but also to other antimicrobials. An alarming increase in antibiotic resistance spreading among pathogenic bacteria inclines to search for alternative therapeutic options, for which resistance can not be developed easily. Among others, photodynamic inactivation (PDI) of S. aureus is a promising option. Photodynamic inactivation is based on a concept that a non toxic chemical, called a photosensitizer upon excitation with light of an appropriate wavelength is activated. As a consequence singlet oxygen and other reactive oxygen species (e.g. superoxide anion) are produced, which are responsible for the cytotoxic effect towards bacterial cells. As strain-dependence in photodynamic inactivation of S. aureus was observed, determination of the molecular marker(s) underlying the mechanism of the bacterial response to PDI treatment would be of great clinical importance. We examined the role of superoxide dismutases (Sod) in photodynamic inactivation of S. aureus as enzymes responsible for oxidative stress resistance.ResultsThe effectiveness of photodynamic inactivation towards S. aureus and its Sod isogenic mutants deprived of either of the two superoxide dismutase activities, namely SodA or SodM or both of them showed similar results, regardless of the Sod status in TSB medium. On the contrary, in the CL medium (without Mn++ ions) the double SodAM mutant was highly susceptible to photodynamic inactivation. Among 8 clinical isolates of S. aureus analyzed (4 MRSA and 4 MSSA), strains highly resistant and strains highly vulnerable to photodynamic inactivation were noticed. We observed that Sod activity as well as sodA and sodM transcript level increases after protoporphyrin IX-based photodynamic treatment but only in PDI-sensitive strains.ConclusionsWe confirmed that porphyrin-based photokilling efficacy is a strain-dependent phenomenon. We showed that oxidative stress sensitivity caused by the lack of both Sod enzymes can be relieved in the presence of Mn ions and partially in the presence of Fe ions. The fact that Sod activity increase is observed only in PDI-susceptible cells emphasizes that this is probably not a direct factor affecting S. aureus vulnerability to porphyrin-based PDI.

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“…), their tedious synthesis, poor bioavailability, and prolonged patient photosensitivity has limited their application. Thus, there is rising interest in the investigation of alternative structural motifs to develop next-generation PSs, with notable examples including various phenothiazinium derivatives, anthracyclines and anthraquinones (e.g., hypericin and doxorubicin), − xanthenes, , cyanine , and BODIPY dyes, and ruthenium, − rhodium, rhenium, − and lanthanide complexes. − Metal complexes are particularly suitable for this task, as the inclusion of a metal into the PS takes advantage of the heavy atom effect to populate the excited triplet state of the PS ( 3 PS*), which in turn facilitates generation of ROS and, ultimately, cell death.…”

Section: Introductionmentioning

confidence: 99%

“…Only more recently have the unique physical and chemical properties of the lanthanides begun to be exploited in the development of PDT agents . Indeed, lanthanide-substituted porphyrins and porphyrin analogues make promising PSs for use in PDT, and the number of reports in this area has steadily increased. − The most successful of these include the diamagnetic lutetium(III) texaphyrin complex (MLu, Lutrin, Figure ), a remarkable compound that can be excited at 732 nm and is currently undergoing clinical trials for breast cancer and photoangioplasty. − Others have implemented lanthanides in doped nanoparticles to overcome issues with stability of the PS and for tumor-targeted drug delivery . In particular, lanthanide-doped upconverting nanoparticles (UCNPs) have gained immense interest for near-IR-triggered PDT. ,, However, nanoparticles in general suffer poor translation to clinical application due to difficulties in the modulation of their biodistribution, which results in poor net delivery to solid tumors (<1%), while biological barriers and off-target accumulation lead to undesired toxicities …”

Section: Introductionmentioning

confidence: 99%

Extending the Excitation Wavelength of Potential Photosensitizers via Appendage of a Kinetically Stable Terbium(III) Macrocyclic Complex for Applications in Photodynamic Therapy

et al. 2017

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The development of viable photodynamic therapy protocols is often hindered by photosensitizers that require high-energy UV irradiation that has limited potential for clinical use due to its low tissue penetration. Herein, we report a strategy for extending the excitation wavelength of potential photosensitizers via the covalent attachment of a terbium(III)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetate complex (DO3A-Tb). The method was systematically demonstrated with a series of polycyclic aromatic hydrocarbons (naphthalene, phenanthrene, anthracene, pyrene, and fluoranthene) to prepare six new complexes (Tb1-Tb6) with bathochromic shifts that extended into the visible region. Determination of their quantum yields for singlet oxygen (O) production at 350 and 420 nm showed significant enhancements from the parent molecule in all cases. Cell viability studies on cervical cancer cells (HeLa) and noncancerous MRC-5 cells showed no measurable cytotoxicity for all complexes prior to light irradiation. However, after irradiation at 420 nm (20 min, 9.27 J cm), Tb3-Tb6 were phototoxic to HeLa cells with IC values between 14.3-32.3 μM. Cell morphological studies and fluorescence microscopy with live/dead cell stains confirmed these findings. In addition, these complexes were highly stable in human blood plasma, with no significant degradation observed after 96 h at 37 °C. This excellent phototoxicity profile and high stability in blood plasma, coupled with the moderately lipophilic nature of the complexes, favorably indicate the potential of DO3A-Tb as a heavy atom-bearing moiety for modification of potential photosensitizers into ideal phototherapeutic drug candidates with longer excitation wavelengths for in vivo application.

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Photodynamic effect of lanthanide derivatives of meso-tetra(N-methyl-4-pyridyl)porphine against Staphylococcus aureus.

Cited by 10 publications

References 17 publications

Staphylococcus aureus as an infectious agent: overview of biochemistry and molecular genetics of its pathogenicity.

Staphylococcus aureus as an infectious agent: overview of biochemistry and molecular genetics of its pathogenicity.

Superoxide dismutase is upregulated in Staphylococcus aureus following protoporphyrin-mediated photodynamic inactivation and does not directly influence the response to photodynamic treatment

Extending the Excitation Wavelength of Potential Photosensitizers via Appendage of a Kinetically Stable Terbium(III) Macrocyclic Complex for Applications in Photodynamic Therapy

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