Laser NIR Irradiation Enhances Antimicrobial Photodynamic Inactivation of Biofilms of Staphylococcus aureus.

OBJECTIVES: Photodynamic inactivation (PDI) is a powerful technique for eradicating microorganisms, and our group previously demonstrated its effectiveness against planktonic cultures of Staphylococcus aureus bacteria using 5,10,15,20-tetrakis[4-(3-N,N-dimethylaminopropoxy)phenyl]porphyrin (TAPP) and visible light irradiation. However, biofilms exhibit a lower sensitivity to PDI, mainly due to limited penetration of the photosensitizer (PS). In the context of emerging antibacterial strategies, near-infrared treatments (NIRTs) have shown promise, especially for combating resistant strains. NIRT can act either through photon absorption by water, causing a thermal effect on bacteria, or by specific chromophores without a significant temperature increase. Our objective was to enhance biofilm sensitivity to TAPP-PDI by pretreatment with NIRT. This combined approach aims to disrupt biofilms and increase the efficacy of TAPP-PDI against bacterial biofilms. MATERIALS AND METHODS: In vitro biofilm models of S. aureus RN6390 were utilized. NIRTs involved a 980 nm laser (continuous mode, 7.5 W/cm2, 30 s, totaling 225 J/cm2) post-TAPP exposure to enhance photosensitizer accumulation. Subsequent visible light irradiation at 180 J/cm2 was employed to perform PDI. Colony-forming unit counts evaluated the synergistic effect on bacterial viability. Scanning electron microscopy visualized the architectural changes in the biofilm structure. TAPP was extracted from bacteria to estimate the impact of NIRT on biofilm penetration. RESULTS: Using in vitro biofilm models, NIRT application following biofilm exposure to TAPP increased PS accumulation per bacteria. Under these conditions, NIRT induced a transient increase in the temperature of PBS to 46.0 ± 2.6°C (ΔT = 21.5°C). Following exposure to visible light, a synergistic effect emerged, yielding a substantial 4.4 ± 0.1-log CFU reduction. In contrast, the PDI and NIRT treatments individually caused a decrease in viability of 0.9 ± 0.1 and 0.8 ± 0.2-log respectively. Interestingly, preheating TAPP-PBS to 46°C had no significant impact on TAPP-PDI efficacy, suggesting the involvement of thermal and nonthermal effects of NIR action. In addition to the enhanced TAPP penetration, NIRT dispersed the biofilms and induced clefts in the biofilm matrix. CONCLUSION: Our findings suggest that NIR irradiation serves as a complementary treatment to PDI. This combined strategy reduces bacterial numbers at lower PS concentrations than standalone PDI treatment, highlighting its potential as an effective and resource-efficient antibacterial approach.

Modulating the phototoxicity and selectivity of a porphyrazine towards epidermal tumor cells by coordination with metal ions.

Porphyrazines (Pzs) are porphyrin derivatives that show potential application as photosensitizers for photodynamic therapy (PDT), but are still far less explored in the literature. In this work, we evaluate how the photophysics and phototoxicity of the octakis(trifluoromethylphenyl)porphyrazine (H2Pz) against tumor cells can be modulated by coordination with Mg(II), Zn(II), Cu(II) and Co(II) ions. Fluorescence and singlet oxygen quantum yields for the Pzs were measured in organic solvents and in soy phosphatidylcholine (PC) liposomes suspended in water. While H2Pz and the respective complexes with Cu(II) and Co(II) showed very low efficiency to fluoresce and to produce 1O2, the Mg(II) and Zn(II) complexes showed significantly higher quantum yields in organic solvents. The fluorescence of these two Pzs in the liposomes was sensitive to the fluidity of the membrane, showing potential use as viscosity markers. The cytotoxicity of the compounds was tested in HaCaT (normal) and A431 (tumor) cells using soy PC liposomes as drug carriers. Despite the low 1O2 quantum yields in water, the Mg(II) and Zn(II) complexes showed IC50 values against A431 cells in the nanomolar range when activated with low doses of red LED light. Their phototoxicity was ca. three times higher for the tumor cells compared to the normal ones, showing promising application as photosensitizers for PDT protocols. Considering that H2Pz and the respective Co(II) and Cu(II) complexes were practically non-phototoxic to the cells, we demonstrate the importance of the central metal ion in the modulation of the photodynamic activity of porphyrazines.

Multiple PDT sessions with chlorin-e6 and LL-37 loaded-nanoemulsion provide limited benefits to periodontitis in rats.

BACKGROUND: The combination of photodynamic therapy (PDT) and LL-37 has never been tested in an animal study and our research team background suggests this strategy might be a promising alternative to intensify periodontitis resolution. This study aimed to assess the effects of multiple sessions of PDT with chlorin-e6 conjugated to the antimicrobial peptide LL-37 loaded nanoemulsion, as adjunctive therapy in experimental periodontitis in rats. METHODS: Experimental periodontitis was induced in 81 rats. After disease establishment, animals were assigned to three groups: SRP (scaling and root planning); SRP + 1PDT, SRP followed by a single PDT session; SRP + 4PDT (n = 27), SRP followed by four PDT sessions at 0, 24, 48 and 72 h after SRP. Animals were subjected to euthanasia at 7, 14 and 28 days, and samples were submitted to osteoclast quantification, immunological and microtomography analysis. RESULTS: All treatments resulted in significant periodontal improvements and there was no significant difference between the groups in both local inflammatory response and healing process. Minimal adjunctive effects could be found for the combined therapy in terms of cytokine levels (IL-1ß and IL-10), with no statistical significance. However, the number of TRAP-positive osteoclasts per mm of alveolar bone linear surface for the group treated with PDT sessions was significantly lower than those treated with SRP only. CONCLUSIONS: Multiple PDT sessions with chlorin-e6 and LL-37 nanoemulsion as an adjunct to scaling and root planning reduced the presence of osteoclast in the local site but did not contribute towards bone regeneration and IL-1ß and IL-10 levels.

In vitro antimicrobial, antibiofilm photodynamic activity, and molecular dynamic simulations of tetra-cationic porphyrinmembrane interactions against foodborne microorganisms.

This manuscript presents a new report on the in vitro antimicrobial photo-inactivation of foodborne microorganisms (Salmonella spp. and Listeria monocytogenes) using tetra-cationic porphyrins. Isomeric tetra-cationic porphyrins (3MeTPyP, 4MeTPyP, 3PtTPyP, and 4PtTPyP) were tested, and antimicrobial activity assays were performed at specific photosensitizer concentrations under dark and white-light LED irradiation conditions. Among the tested bacterial strains, 4MeTPyP exhibited the highest efficiency, inhibiting bacterial growth within just 60 min at low concentrations (17.5 µM). The minimal inhibitory concentration of 4MeTPyP increased when reactive oxygen species scavengers were present, indicating the significant involvement of singlet oxygen species in the photooxidation mechanism. Furthermore, the checkerboard assay testing the association of 4MeTPyP showed an indifferent effect. Atomic force microscopy analyses and dynamic simulations were conducted to enhance our understanding of the interaction between this porphyrin and the strain's membrane.

Morphological aspects and the effectiveness of photodynamic inactivation against Rhizopus oryzae in different life cycles.

Mucormycosis is an extremely aggressive fungal disease with a high mortality rate, especially in people with compromised immune systems. Most cases of mucormycosis are caused by the fungus Rhizopus oryzae. The treatments used are based on high doses of antifungals, associated with surgical resections, when it is possible. However, even with this aggressive treatment, the estimated attributable mortality rate is high. There is therefore a need to develop adjuvant treatments. Photodynamic Inactivation (PDI) may be an auxiliary therapeutic option for mucormycosis. Due to the lack of reports in the literature on the morphology and photodynamic inactivation of R. oryzae, characterization of the fungus using Confocal Microscopy and Transmission Electron Microscopy, and different protocols using Photodithazine® (PDZ), a chlorin e6 compound, as a photosensitizer, were performed. The fungus growth rate under different concentrations and incubation times of the photosensitizer and its association with the surfactant Sodium Dodecyl Sulphate (SDS) was evaluated. For the hyphae, both in the light and dark phases, in the protocols using only PDZ, no effective photodynamic response was observed. Meanwhile with the combination of SDS 0.05% and PDZ, inhibition growth rates of 98% and 72% were achieved for the white and black phase, respectively. In the conidia phase, only a 1.7 log10 reduction of the infective spores was observed. High concentration of melanin and the complex and resistant structures, especially at the black phase, results in a high limitation of the PDI inactivation response. The combined use of the SDS resulted in an improved response, when compared to the one obtained with the amphotericin B treatment.

The effect of light irradiation on a nitro-ruthenium porphyrin complex in the induced death of lung cancer cells in two- and three-dimensional cultures: Insights into the effect of nitric oxide.

Efforts to find compounds selectively affecting cancer cells while sparing normal ones have continued to grow. Nitric oxide (NO) is critical in physiology and pathology, including cancer. It influences cellular processes like proliferation, apoptosis, and angiogenesis. The intricate interaction of NO with cancer cells offers innovative treatment possibilities, but its effects can vary by concentration and site. Ruthenium complexes capable of releasing NO upon stimulation show for this purpose. These versatile compounds can also enhance photodynamic therapy (PDT), a light-activated approach, which induces cellular damage. Ruthenium-based photosensitizers (PSs), delivering NO and producing reactive oxygen species (ROS), offer a novel strategy for improved cancer treatments. In this study, a nitro-ruthenium porphyrin conjugate: {TPyP[Ru(NO2)(bpy)2]4}(PF6)4, designated RuNO2TPyP, which releases NO upon irradiation, was investigated for its effects on lung cells (non-tumor MRC-5 and tumor A549) in 2D and 3D cell cultures. The findings suggest that this complex has potential for PDT treatment in lung cancer, as it exhibits photocytotoxicity at low concentrations without causing cytotoxicity to normal lung cells. Moreover, treatment of cells with RuNO2TPyP followed by light irradiation (4 J cm-2) can induce apoptosis, generate ROS, promote intracellular NO formation, and has anti-migratory effects. Additionally, the complex can modify tumor cell structures and induce photocytotoxicity and apoptosis in a 3D culture. These outcomes are attributed to the internalization of the complex and its subsequent activation upon light irradiation, resulting in NO release and singlet oxygen production.

Evaluation of quantification methods to determine photodynamic action on mono- and dual-species bacterial biofilms.

The effect of photodynamic inactivation (PDI) sensitized by 5,10,15,20-tetra(4-N,N,N-trimethylammoniophenyl)porphyrin (TMAP4+) on different components of mono- and dual-species biofilms of Staphylococcus aureus and Escherichia coli was determined by different methods. First, the plate count technique showed that TMAP4+-PDI was more effective on S. aureus than E. coli biofilm. However, crystal violet staining revealed no significant differences between before and after PDI biofilms of both bacteria. On the other hand, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method indicated a reduction in viable cells as the light exposure time increases in both, mono- and dual-species biofilms. Furthermore, it was determined that as the irradiation time increases, the amount of extracellular polymeric substances present in the biofilms decreased. This effect was presented in both strains and in the mixed biofilm, being more evident in S. aureus mono-specie biofilm. Finally, scanning electron microscopy analysis showed a decrease in the number of cells forming the biofilm after photosensitization treatments. This information makes it possible to determine whether the photodynamic action is based on damage to metabolic activity, extracellular matrix and/or biomass, which may be useful in establishing a fully effective PDI protocol for the treatment of microorganisms growing as biofilms.

Specific photodamage on HT-29 cancer cells leads to endolysosomal failure and autophagy blockage by cathepsin depletion.

Endolysosomes perform a wide range of cellular functions, including nutrient sensing, macromolecule digestion and recycling, as well as plasma membrane repair. Because of their high activity in cancerous cells, endolysosomes are attractive targets for the development of novel cancer treatments. Light-activated compounds termed photosensitizers (PS) can catalyze the oxidation of specific biomolecules and intracellular organelles. To selectively damage endosomes and lysosomes, HT-29 colorectal cancer cells were incubated with nanomolar concentrations of meso-tetraphenylporphine disulfonate (TPPS2a), an amphiphilic PS taken up via endocytosis and activated by green light (522 nm, 2.1 J.cm-1). Several cellular responses were characterized by a combination of immunofluorescence and immunoblotting assays. We showed that TPPS2a photosensitization blocked autophagic flux without extensive endolysosomal membrane rupture. Nevertheless, there was a severe functional failure of endolysosomes due to a decrease in CTSD (cathepsin D, 55%) and CTSB (cathepsin B, 52%) maturation. PSAP (prosaposin) processing (into saposins) was also considerably impaired, a fact that could be detrimental to glycosphingolipid homeostasis. Therefore, photosensitization of HT-29 cells previously incubated with a low concentration of TPPS2a promotes endolysosomal dysfunction, an effect that can be used to improve cancer therapies.

The photophysical, photobiological, and DNA/HSA-binding properties of corroles containing carbazole and phenothiazine moieties.

This study characterized four corrole derivatives, namely Cbz-Cor, MetCbz-Cor, PTz-Cor, and PTzEt-Cor, examining their photophysical, electrochemical, photobiological, and biomolecule-binding properties. Experimental photophysical data of absorption and emission elements correlated with a theoretical analysis obtained through time-dependent density functional theory (TD-DFT). As for the photophysical properties, we observed lower fluorescence quantum yields and discernible differences between the excited and ground states, as indicated by Stokes shift values. Natural Transition Orbit (NTO) plots presented high occupied molecular orbital - low unoccupied molecular orbital (HOMO-LUMO) densities around the tetrapyrrolic macrocycle in all examples. Our findings demonstrate that corroles maintain stability in solution and offer photostability (<20 %), predominantly in DMSO(5 %)/Tris-HCl (pH 7.4) buffer solution. Furthermore, the singlet oxygen (1O2) quantum yield and log POW values underscore their potential application in photoinactivation approaches, as these corroles serve as effective ROS generators with more lipophilic features. We also evaluated their biomolecular binding capacity towards salmon sperm DNA and human serum albumin using spectroscopic techniques and molecular docking analysis for sustenance. Concerning biomolecule interaction profiles, the corrole derivatives showed a propensity for interacting in the minor grooves of the double helix DNA due to secondary forces, which were more pronounced in site III of the human serum protein.

Size-Dependent Blue Emission from Europium-Doped Strontium Fluoride Nanoscintillators for X-Ray-Activated Photodynamic Therapy.

Successful implementation of X-ray-activated photodynamic therapy (X-PDT) is challenging because most photosensitizers (PSs) absorb light in the blue region, but few nanoscintillators produce efficient blue scintillation. Here, efficient blue-emitting SrF2:Eu scintillating nanoparticles (ScNPs) are developed. The optimized synthesis conditions result in cubic nanoparticles with ≈32 nm diameter and blue emission at 416 nm. Coating them with the meso-tetra(n-methyl-4-pyridyl) porphyrin (TMPyP) in a core-shell structure (SrF@TMPyP) results in maximum singlet oxygen (1O2) generation upon X-ray irradiation for nanoparticles with 6TMPyP depositions (SrF@6TMPyP). The 1O2 generation is directly proportional to the dose, does not vary in the low-energy X-ray range (48-160 kVp), but is 21% higher when irradiated with low-energy X-rays than irradiations with higher energy gamma rays. In the clonogenic assay, cancer cells treated with SrF@6TMPyP and exposed to X-rays present a significantly reduced survival fraction compared to the controls. The SrF2:Eu ScNPs and their conjugates stand out as tunable nanoplatforms for X-PDT due to the efficient blue emission from the SrF2:Eu cores; the ability to adjust the scintillation emission in terms of color and intensity by controlling the nanoparticle size; the efficient 1O2 production when conjugated to a PS and the efficacy of killing cancer cells.

Porphyrin-BODIPY Dyad: Enhancing Photodynamic Inactivation via Antenna Effect.

A porphyrin-BODIPY dyad (P-BDP) was obtained through covalent bonding, featuring a two-segment design comprising a light-harvesting antenna system connected to an energy acceptor unit. The absorption spectrum of P-BDP resulted from an overlap of the individual spectra of its constituent parts, with the fluorescence emission of the BODIPY unit experiencing significant quenching (96 %) due to the presence of the porphyrin unit. Spectroscopic, computational, and redox investigations revealed a competition between photoinduced energy and electron transfer processes. The dyad demonstrated the capability to sensitize both singlet molecular oxygen and superoxide radical anions. Additionally, P-BDP effectively induced the photooxidation of L-tryptophan. In suspensions of Staphylococcus aureus cells, the dyad led to a reduction of over 3.5 log (99.99 %) in cell survival following 30 min of irradiation with green light. Photodynamic inactivation caused by P-BDP was also extended to the individual bacterium level, focusing on bacterial cells adhered to a surface. This dyad successfully achieved the total elimination of the bacteria upon 20 min of irradiation. Therefore, P-BDP presents an interesting photosensitizing structure that takes advantage of the light-harvesting antenna properties of the BODIPY unit combined with porphyrin, offering potential to enhance photoinactivation of bacteria.

Antimicrobial activity of cationic water-soluble porphyrin against multidrug-resistant bacteria in biofilms and canine skin samples.

Multidrug-resistant (MDR) microorganisms pose a threat to animal health, particularly in integumentary diseases, which can be caused by multiple organisms and often manifest as biofilms, hindering treatment effectiveness. We evaluated the antimicrobial activity of antimicrobial photodynamic therapy (aPDT) using a water-soluble tetra-cationic porphyrin (4-H2TMeP) against MDR bacteria cultured in biofilm and in mono and polyculture grown on canine skin samples. We utilized 4-H2TMeP porphyrin against MDR Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus pseudintermedius. A non-cytotoxic concentration of 4-H2TMeP (40 µM), previously shown to be effective in vitro against these bacteria cultured in solution, was employed. Biofilms were treated with 4-H2TMeP and subjected to light irradiation for 30, 60, and 90 min. Monocultures on canine skin samples were treated with 4-H2TMeP and irradiated for 30 (S. pseudintermedius), 60 (E. coli), or 60 and 90 min (P. aeruginosa). Polycultures of S. pseudintermedius and E. coli were treated with light for 60 and 90 min. The efficacy of aPDT was evaluated by plating light-exposed biofilms, mono and polycultures of bacteria obtained from skin samples exposed to light and kept in the dark. Colony-forming units were counted after 24 h of incubation at 37 °C. aPDT using 4-H2TMeP reduced bacterial concentrations of S. pseudintermedius and E. coli biofilms. Additionally, it significantly reduced bacterial concentrations cultivated on skin samples, with a particular emphasis on S. pseudintermedius. These findings indicate that aPDT with 4-H2TMeP is a promising alternative treatment against MDR bacteria in animal skin infections and should be further explored through in vivo research.

Advances in porphyrins and chlorins associated with polysaccharides and polysaccharides-based materials for biomedical and pharmaceutical applications.

Over the last decade, the convergence of advanced materials and innovative applications has fostered notable scientific progress within the biomedical and pharmaceutical fields. Porphyrins and their derivatives, distinguished by an extended conjugated π-electron system, have a relevant role in propelling these advancements, especially in drug delivery systems, photodynamic therapy, wound healing, and (bio)sensing. However, despite their promise, the practical clinical application of these macrocycles is hindered by their inherent challenges of low solubility and instability under physiological conditions. To address this limitation, researchers have exploited the synergistic association of porphyrins and chlorins with polysaccharides by engineering conjugated systems and composite/hybrid materials. This review compiles the principal advances in this growing research field, elucidating fundamental principles and critically examining the applications of such materials within biomedical and pharmaceutical contexts. Additionally, the review addresses the eventual challenges and outlines future perspectives for this poignant research field. It is expected that this review will serve as a comprehensive guide for students and researchers dedicated to exploring state-of-the-art materials for contemporary medicine and pharmaceutical applications.

Photoinactivation of microorganisms using bacteriochlorins as photosensitizers.

In recent years, some microorganisms have shown resistance to conventional treatments. Considering this increase in resistant pathogens, treatment alternatives are needed to promote greater treatment efficiency. In this sense, antimicrobial photodynamic therapy (aPDT) has been an alternative treatment. This technique uses a photosensitizer that is activated by light with a specific wavelength producing reactive species, leading to the death of pathogenic microorganisms. In this study, bacteriochlorophyll derivatives such as bacteriochlorin metoxi (Bchl-M) and bacteriochlorin trizma (Bchl-T) obtained from purple bacterium (Rhodopseudomonas faecalis), were evaluated as photosensitizers in the aPDT. Photodynamic inactivation (PDI) of the microorganisms Staphylococcus aureus, Micrococcus luteus, Candida albicans and Pseudomonas aeruginosa was investigated with both bacteriochlorins (Bchl-M and Bchl-T) at different concentrations (1, 15 and 30 µM for S. aureus; 1, 15, 30, 45, 60 and 75 µM for M. luteus; 30, 60, 90, 105, 120 and 150 µM for C. albicans; and 200 µM for P. aeruginosa) and different doses of light (20 and 30 J/cm2 for S. aureus and M. luteus; 30 and 45 J/cm2 for C. albicans; and 45 J/cm2 for P. aeruginosa) to inactivate them. Both photosensitizers showed good activation against S. aureus and for M. luteus, we observed the inactivation of these microorganisms at approximately 3 log, showing to be a good photosensitizers for these microorganisms.

Hydrogen bioelectrogeneration with pH-resilient and oxygen-tolerant cobalt apoenzyme-saccharide.

Hydrogenases are enzymes that catalyze the reversible conversion of protons to hydrogen gas, using earth-abundant metals such as nickel and/or iron. This characteristic makes them promising for sustainable energy applications, particularly in clean hydrogen production. However, their widespread use faces challenges, including a limited pH range and susceptibility to oxygen. In response to these issues, SacCoMyo is introduced as an artificial enzyme. SacCoMyo is designed by replacing the native metal in the myoglobin (Myo) scaffold with a hydroxocobalamin (Co) porphyrin core and complemented by a protective heteropolysaccharide-linked (Sac) shell. This engineered protein proves to be resilient, maintaining robust functionality even in acidic environments and preventing denaturation in a pH 1 electrolyte. The cobalt porphyrin core of SacCoMyo reduces the activation overpotential for hydrogen generation. A high turnover frequency of about 2400 H2 s-1 is demonstrated in the presence of molecular oxygen, showcasing its potential in biohydrogen production and its ability to overcome the limitations associated with natural hydrogenases.

Daylight photodynamic inactivation of cattle tick Rhipicephalus microplus by porphyrins: An alternative for the ectoparasite control.

The bovine tick Rhipicephalus microplus, a primary ectoparasite of veterinary concern, contributes significantly to disease transmission and reduced cattle productivity, resulting in substantial economic losses. The overuse of chemical acaricides has led to the emergence of resistant strains, posing a considerable challenge to veterinary medicine. Consequently, the development of alternative parasite control methods is essential to ensure livestock quality and enhance food safety worldwide. Our study introduces an innovative approach to photodynamic inactivation (PDI) of the bovine tick, harnessing natural daylight for a potential field application. Reproductive parameters (female and egg mass, egg production index, and larval hatch) were evaluated in engorged female ticks under photodynamic action using the hematoporphyrin (HP) and tetra-cationic porphyrins free-base meso-tetra-ruthenated (4-pyridyl) (RuTPyP) and its zinc(II) complex (ZnRuTPyP) as photosensitizers (PS). The results showed that there was no significant difference between the groups treated with tetra­ruthenium porphyrins and the control group. However, HP exhibits a control percentage of 97.9% at a concentration of 2.5 µmol.L-1, aligning with the expected control rates achieved by conventional chemical acaricides. Photophysical and physicochemical parameters such as the number of singlet oxygen produced and lipophilicity were discussed for each PS and related to tick control percentages. Furthermore, the interaction between HP and chitin, an important macromolecule presents in the tick's cuticle, considered as the primary target tick structure during PDI was observed by the absorption and fluorescence emission spectroscopic techniques. Therefore, the results presented here extend the potential for controlling R. microplus through photodynamic inactivation while utilizing sunlight as a source of natural irradiation.

Photophysical, photobiological, and mycobacteria photo-inactivation properties of new meso-tetra-cationic platinum(II) metalloderivatives at meta position.

In this manuscript, we report the photo-inactivation evaluation of new tetra-cationic porphyrins with peripheral Pt(II) complexes ate meta N-pyridyl positions in the antimicrobial photodynamic therapy (aPDT) of rapidly growing mycobacterial strains (RGM). Four different metalloderivatives were synthetized and applied. aPDT experiments in the strains of Mycobacteroides abscessus subsp. Abscessus (ATCC 19977), Mycolicibacterium fortuitum (ATCC 6841), Mycobacteroides abscessus subsp. Massiliense (ATCC 48898), and Mycolicibacterium smegmatis (ATCC 700084) conducted with adequate concentration of photosensitizers (PS) under white-light conditions at 90 min (irradiance of 50 mW cm-2 and a total light dosage of 270 J cm-2) showed that the Zn(II) derivative is the most effective PS significantly reduced the concentration of viable mycobacteria. The effectiveness of the molecule as PS for PDI studies is also clear with mycobacteria, which is strongly related with the porphyrin peripheral charge and coordination platinum(II) compounds and consequently about the presence of metal center ion. This class of PS may be promising antimycobacterial aPDT agents with potential applications in medical clinical cases and bioremediation.

Dosagem de porfobilinogênio urinário para confirmação diagnóstica ou prognóstico de porfirias hepáticas agudas / Dosage of urinary porphobilinogen for diagnostic confirmation or prognosis of acute hepatic porphyrias

INTRODUÇÃO: As porfirias são distúrbios metabólicos raros hereditários ou adquiridos em que há uma deficiência parcial ou completa em uma das oito enzimas da via de biossíntese do heme, que é grupo prostético que consiste de um átomo de ferro contido no centro de um largo anel orgânico heterocíclico. Esse grupo tem importância biológica por ser grupo prostético de proteínas, conhecidas como hemeproteínas. Com base no tecido afetado, as porfirias podem ser classificadas como eritropoiéticas ou hepáticas e, com base na apresentação dos sintomas, podem ser classificadas como porfirias hepáticas agudas (PHA) ou cutâneas. Os testes de primeira linha recomendados para diagnóstico da PHA incluem dosagem de PBG (dPBG; análise quantitativa), ácido delta-aminolevulinico (ALA) e porfirinas em uma amostra de urina aleatória. Atualmente, há disponível no SUS apenas o procedimento para a realização da pesquisa de PBG urinário (pPBGu; análise qualitativa). Tendo em vista a recorrência de falso-positivos ou falso-negativos provenientes da pPBGu urinário, foram analisadas as evidências científicas dis

DNA-Interactive and Damage Study with meso-Tetra(2-thienyl)porphyrins Coordinated with Polypyridyl Pd(II) and Pt(II) Complexes.

We report the DNA-binding properties of three porphyrins with peripheral thienyl substituents (TThPor, PdTThPor and PtTThPor). The binding capacity of each porphyrin with DNA was determined by UV-Vis and steady-state fluorescence emission spectroscopy combined with molecular docking calculations. The results suggest that the interaction of these compounds probably occurs via secondary interactions via external grooves (minor grooves) around the DNA macromolecule. Moreover, porphyrins containing peripheral Pd(II) or Pt(II) complexes (PdTThPor and PtTThPor) were able to promote photo-damage in the DNA.

Photosensitizers combination approach to enhance photodynamic inactivation of planktonic and biofilm bacteria.

To improve bacterial photodynamic inactivation (PDI), this work analyzes the photodynamic effect caused by the combination of photosensitizers (PSs) on two bacterial models and different growth mode. Simultaneous administration of PSs from different families, zinc(II) 2,9,16,23-tetrakis[4-(N-methylpyridyloxy)]phthalocyanine (ZnPPc4+), 5,10,15,20-tetra(4-N,N,N-trimethylammonium phenyl)porphyrin (TMAP4+), meso-tetrakis(9-ethyl-9-methyl-3-carbazoyl)chlorin (TEMCC4+) and 5,10,15,20-tetrakis[4-(3-N,N-dimethylaminopropoxy)phenyl] chlorin (TAPC) was investigated against Staphylococcus aureus and Escherichia coli, in planktonic form, biofilm and growth curve. Various PSs combinations showed greater inactivation compared to when used separately under the same conditions but at twice the concentration. However, differences were found in the effectiveness of the PSs combinations on Gram positive and negative bacteria, as well as in planktonic or biofilm form. Likewise, the combination of three PSs completely stopped E. coli growth under optimal nutritional conditions. PSs combination allows extending the range of light absorption by agents that absorb in different areas of the visible spectrum. Therefore, PDI with combined PSs increases its antimicrobial capacity using agents' concentrations and light fluences lower than those necessary to cause the same effect as single PS. These advances represent a starting point for future research on the potentiation of PDI promoted by the combined use of PSs.