Showing papers by "Maria A. F. Faustino published in 2022"

Photoinactivation of Phage Phi6 as a SARS-CoV-2 Model in Wastewater: Evidence of Efficacy and Safety

Abstract: The last two years have been marked by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. This virus is found in the intestinal tract; it reaches wastewater systems and, consequently, the natural receiving water bodies. As such, inefficiently treated wastewater (WW) can be a means of contamination. The currently used methods for the disinfection of WW can lead to the formation of toxic compounds and can be expensive or inefficient. As such, new and alternative approaches must be considered, namely, photodynamic inactivation (PDI). In this work, the bacteriophage φ6 (or, simply, phage φ6), which has been used as a suitable model for enveloped RNA viruses, such as coronaviruses (CoVs), was used as a model of SARS-CoV-2. Firstly, to understand the virus’s survival in the environment, phage φ6 was subjected to different laboratory-controlled environmental conditions (temperature, pH, salinity, and solar and UV-B irradiation), and its persistence over time was assessed. Second, to assess the efficiency of PDI towards the virus, assays were performed in both phosphate-buffered saline (PBS), a commonly used aqueous matrix, and a secondarily treated WW (a real WW matrix). Third, as WW is generally discharged into the marine environment after treatment, the safety of PDI-treated WW was assessed through the determination of the viability of native marine water microorganisms after their contact with the PDI-treated effluent. Overall, the results showed that, when used as a surrogate for SARS-CoV-2, phage φ6 remains viable in different environmental conditions for a considerable period. Moreover, PDI proved to be an efficient approach in the inactivation of the viruses, and the PDI-treated effluent showed no toxicity to native aquatic microorganisms under realistic dilution conditions, thus endorsing PDI as an efficient and safe tertiary WW disinfection method. Although all studies were performed with phage φ6, which is considered a suitable model of SARS-CoV-2, further studies using SARS-CoV-2 are necessary; nevertheless, the findings show the potential of PDI for controlling SARS-CoV-2 in WW.

The Antimicrobial Photoinactivation Effect on Escherichia coli through the Action of Inverted Cationic Porphyrin–Cyclodextrin Conjugates

Abstract: Photodynamic action has been used for diverse biomedical applications, such as treating a broad range of bacterial infections. Based on the combination of light, dioxygen, and photosensitizer (PS), the photodynamic inactivation (PDI) approach led to the formation of reactive oxygen species (ROS) and represented a non-invasive, non-toxic, repeatable procedure for pathogen photoinactivation. To this end, different tetrapyrrolic macrocycles, such as porphyrin (Por) dyes, have been used as PSs for PDI against microorganisms, mainly bacteria. Still, there is significant room for improvement, especially new PS molecules. Herein, unsymmetrical new pyridinone (3–5) and thiopyridyl Pors (7) were prepared with α-, β-, or γ-cyclodextrin (CD) units, following their quaternization to perform the corresponding free-base Pors (3a–5a and 7a), and were compared with the already-known Pors 6a and 8a, both bearing thiopyridinium and CD units. These water-soluble porphyrins were evaluated as PSs, and their photophysical and photochemical properties and photodynamic effects on E. coli were assessed. The presence of one CD unit and three positive charges on the Por structure (3a–5a and 7a) enhanced their aqueous solubility. The photoactivity of the cationic Pors 3a–5a and 6a–8a ensured their potential against the Gram-negative bacterium E. coli. Within each series of methoxypyridinium vs thiopyridinium dyes, the best PDI efficiency was achieved for 5a with a bacterial viability reduction of 3.5 log10 (50 mW cm−2, 60 min of light irradiation) and for 8a with a total bacterial viability reduction (>8 log10, 25 mW cm−2, 30 min of light irradiation). Here, the presence of the methoxypyridinium units is less effective against E. coli when compared with the thiopyridinium moieties. This study allows for the conclusion that the peripheral charge position, quaternized substituent type/CD unit, and affinity to the outer bacterial structures play an important role in the photoinactivation efficiency of E. coli, evidencing that these features should be further addressed in the pursuit for optimised PS for the antimicrobial PDI of pathogenic microorganisms.

Photodynamic inactivation of pathogenic Gram-negative and Gram-positive bacteria mediated by Si(IV) phthalocyanines bearing axial ammonium units.

Abstract: The photodynamic inactivation (PDI) of microorganisms has gained interest as an efficient option for conventional antibiotic treatments. Recently, Si(IV) phthalocyanines (SiPcs) have been highlighted as promising photosensitizers (PSs) to the PDI of microorganisms due to their remarkable absorption and emission features. To increase the potential of cationic SiPcs as PS drugs, one novel (1a) and two previously described (2a and 3a) axially substituted PSs with di-, tetra-, and hexa-ammonium units, respectively, were synthesized and characterized. Their PDI effect was evaluated for the first time against Escherichia coli and Staphylococcus aureus, a Gram-negative and a Gram-positive bacterium, respectively. The photodynamic treatments were conducted with PS concentrations of 3.0 and 6.0 μM under 60 min of white light irradiation (150 mW.cm-2). The biological results show high photodynamic efficiency for di- and tetra-cationic PSs 1a and 2a (6.0 μM), reducing the E. coli viability in 5.2 and 3.9 log, respectively (after 15 min of dark incubation before irradiation). For PS 3a, a similar bacterial reduction (3.6 log) was achieved but only with an extended dark incubation period (30 min). Under the same experimental conditions, the photodynamic effect of cationic PSs 1a-3a on S. aureus was even more promising, with abundance reductions of ca. 8.0 log after 45-60 min of PDI treatment. These results reveal the high PDI efficiency of PSs bearing ammonium groups and suggest their promising application as a broad-spectrum antimicrobial to control infections caused by Gram-negative and Gram-positive bacteria.

Can Corrole Dimers Be Good Photosensitizers to Kill Bacteria?

Abstract: Corroles possess key photophysical and photochemical properties to be exploited as therapeutic agents in antimicrobial photodynamic therapy (aPDT). Herein, we present for the first time the antimicrobial efficiency of three corrole dimers and of the corresponding precursor against the Gram(+) bacterium Staphylococcus aureus. Additionally, to explore future clinical applications, the cytotoxicity of the most promising derivatives towards Vero cells was evaluated. The aPDT assays performed under white light irradiation (50 mW/cm2; light dose 450 J/cm2) and at a corrole concentration of 15 µM showed that some dimers were able to reduce 99.9999% of S. aureus strain (decrease of 5 log10 CFU/mL) and their photodynamic efficiency was dependent on position, type of linkage, and aggregation behavior. Under the same light conditions, the corrole precursor 1 demonstrated notable photodynamic efficiency, achieving total photoinactivation (>8.0 log10 CFU/mL reduction) after the same period of irradiation (light dose 450 J/cm2). No cytotoxicity was observed when Vero cells were exposed to corrole 1 and dimer 3 for 24 h according to ISO guidelines (ISO 10993-5) for in vitro cytotoxicity of medical devices. The results show that corrole dimers, dependent on their structures, can be considered good photosensitizers to kill Staphylococcus aureus.

Anti-Viral Photodynamic Inactivation of T4-like Bacteriophage as a Mammalian Virus Model in Blood

Abstract: The laboratorial available methods applied in plasma disinfection can induce damage in other blood components. Antimicrobial photodynamic therapy (aPDT) represents a promising approach and is approved for plasma and platelet disinfection using non-porphyrinic photosensitizers (PSs), such as methylene blue (MB). In this study, the photodynamic action of three cationic porphyrins (Tri-Py(+)-Me, Tetra-Py(+)-Me and Tetra-S-Py(+)-Me) towards viruses was evaluated under white light irradiation at an irradiance of 25 and 150 mW·cm−2, and the results were compared with the efficacy of the approved MB. None of the PSs caused hemolysis at the isotonic conditions, using a T4-like phage as a model of mammalian viruses. All porphyrins were more effective than MB in the photoinactivation of the T4-like phage in plasma. Moreover, the most efficient PS promoted a moderate inactivation rate of the T4-like phage in whole blood. Nevertheless, these porphyrins, such as MB, can be considered promising and safe PSs to photoinactivate viruses in blood plasma.

Photoinactivation of Bacterial and Fungal Planktonic/Biofilm Forms Using the Combination of a Porphyrinic Formulation with Potassium Iodide

Abstract: Antimicrobial photodynamic therapy (aPDT) is a promising approach against multidrug-resistant microorganisms. In this work, we accessed the photodynamic efficiency of an affordable formulation composed of five cationic porphyrins (FORM) and its combined effect with potassium iodide (KI) on a large spectrum of microorganisms. For this purpose, the aPDT assays were conducted with FORM alone and FORM + KI on planktonic and biofilm forms of Gram(+) (Staphylococcus aureus) and Gram(−) (Escherichia coli) bacteria and of the yeast Candida albicans. The results obtained indicate that FORM, at low concentrations (0.5–5.0 μM), had an efficient photodynamic action on the planktonic forms of E. coli, S. aureus, and C. albicans. Moreover, the combination of FORM with KI improved the photodynamic action of this PS, promoting microbial inactivation with lower PS concentrations and treatment time. The combination of FORM + KI was also extremely efficient in the destruction of bacterial and fungal biofilms. This outstanding effect may be due to the action of longer-lived iodine reactive species produced by the reaction of KI with the ROS generated by FORM during the aPDT treatment.

Straightforward Synthesis of Thiazolo[5,4-c]isoquinolines from Dithiooxamide and 2-Halobenzaldehydes

Abstract: The reaction of dithiooxamide with aromatic aldehydes is a well-known method for the preparation of thiazolo[5,4-d]thiazoles (TzTz). However, we report here that, using adequately substituted 2-halobenzaldehydes, this reaction may afford...

Synthesis, antioxidant and antitumoral activity of new 5’-arylchalcogenyl-3’-N-(E)-feruloyl-3’, 5’-dideoxy-amino-thymidine (AFAT) derivatives

Abstract: The synthesis of a new class of 5’-arylchalcogenyl-3’-N-(E)-feruloyl-3’-amino-3’-deoxythymidine (AFAT) derivatives is disclosed. The compounds were obtained in good yields through an amidation reaction employing soft conditions. Both antitumoral activity against...

Photodynamic Inactivation of Phage Phi6 as SARS-CoV-2 Model in Wastewater Disinfection: Effectivity and Safety

Abstract: The past 2 years have been marked by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. This virus is found in the intestinal tract and reaches the wastewater system, and, consequently, the natural receiving water bodies, and inappropriate or/and inefficient WW treatment is a means of contamination. In the present work, we used a SARS-CoV-2 model—the phage Phi6—to evaluate its survival under different environmental conditions (pH, temperature, salinity, solar, and UV-B irradiation). Then, we tested the efficiency of photodynamic inactivation (PDI) as a WW disinfection alternative method, and, additionally, the impact on the cultivable native marine microorganisms of the PDI-treated WW was evaluated.

Synthetic Access to Tetracationic Benzoporphyrins and Their Role as Photosensitizers towards Gram-Negative Escherichia coli

Abstract: : Nowadays world population faces an episode where bacteria are becoming resistant to antibiotics, and it is crucial to find out alternatives and new molecules to fight these microorganisms. Photodynamic inactivation of microorganisms has been pointed out as an alternative to conventional therapies. This work describes the synthesis of benzoporphyrins derivatives bearing triazolyl groups and of the analogues with pyridyl units under Heck coupling conditions. The benzoporphyrin derivatives containing pyridyl groups were further quaternized with iodomethane and 1-iodopentane to evaluate the influence of alkyl chain size on their photoinactivation ability. The biological studies towards Gram-negative bioluminescent Escherichia coli showed that the tetracationic benzoporphyrins can efficiently inactivate this bacterium.

Editorial: Next generation nanomaterials for photodynamic therapy

Abstract: Photodynamic therapy (PDT) is a clinically approved treatment for oncologic and non-oncologic diseases and has several advantages over conventional oncological treatments, such as chemotherapy, radiotherapy, and surgery (Dolmans et al., 2003; Correia et al., 2021). The cytotoxic reactive oxygen species (ROS) produced by the interaction of non-toxic photoactivable molecules (photosensitizers) with dioxygen leads to cancer cell death with a good cosmetic outcome (Pham et al., 2021). Despite the good progress made with photosensitizer (PS)-mediated PDT, this treatment modality has some limitations, such as PS aggregation, low solubility in physiological media, and tissue/ cell specificity (Gunaydin et al., 2021). Recently, several studies based on hybrid nanoparticles were conducted to improve the selectivity and PDT outcome of PSs (Babu et al., 2022). These hybrid materials can circumvent the limitations of conventional PS drugs, increasing their solubility in biological media and improving PS uptake in targets (Lim et al., 2013). Thus, there is significant room for improvement in new generations of nanomaterials and PS agents that can bring about a novel generation of PSs. The Research Topic ‘Next generation nanomaterials for photodynamic therapy’ comprises five reviews covering recent developments in the fields of nanomaterials for PDT, mechanistic studies, and improving the targeting of nanoplatforms. Uprety et al. explored the potential of quantum dots (QDs) as PSs for PDT. The versatility of QDs was highlighted, particularly their optical properties, which can be finetuned by varying their size. It is worth mentioning that the main advantage of QDs over conventional PSs is the modulation of emission properties within the near IR, consequently allowing deep-light penetration in cancer tissues. Heavy metal QD OPEN ACCESS

Safety assessment of new nanodiamonds@corrole hybrids addressed by the response of RAW-264.7 macrophages.

Abstract: Safety assessment of carbon nanomaterials is of paramount importance since they are on the frontline for applications in sensing, bioimaging and drug delivery. The biocompatibility and safety of functionalized nanodiamonds (NDs) are here addressed through the study of the pro-inflammatory response of RAW-264.7 macrophages exposed to new nanodiamonds@corrole hybrids. The corrole unit selected is as a prototype for a hydrophobic organic molecule that can function as a NIR fluorophore reporter, an optical sensor, a photodynamic therapy agent or a photocatalyst. The new functional nanohybrids containing detonated nanodiamonds (NDs) were obtained through esterification using carboxylated NDs and glycol corroles. The success of the covalent functionalization via carbodiimide activation was confirmed through X-ray photoelectron spectroscopy (XPS), Raman and Fourier transform infrared (FTIR) spectroscopy. The UV-vis absorption and emission spectra of the hybrids are additive with respect to the corrole features. The cellular uptake, localization, cell viability and effects on immune cell activation of the new hybrids and of the precursors were carefully investigated using RAW-264.7 macrophages. Overall results showed that the ND@corrole hybrids had no pro-inflammatory effects on the RAW-264.7 macrophage cell line, making them an ideal candidate for a wide range of biomedical applications.

New Bis-Cyclometalated Iridium(III) Complexes with β-Substituted Porphyrin-Arylbipyridine as the Ancillary Ligand: Electrochemical and Photophysical Insights

Abstract: An efficient synthetic access to new cationic porphyrin-bipyridine iridium(III) bis-cyclometalated complexes was developed. These porphyrins bearing arylbipyridine moieties at β-pyrrolic positions coordinated with iridium(III), and the corresponding Zn(II) porphyrin complexes were spectroscopically, electrochemically, and electronically characterized. The features displayed by the new cyclometalated porphyrin-bipyridine iridium(III) complexes, namely photoinduced electron transfer process (PET), and a remarkable efficiency to generate 1O2, allowing us to envisage new challenges and opportunities for their applications in several fields, such as photo(catalysis) and photodynamic therapies.