Search Results (21)

Evolving antibiotic resistance of bacteria is a prevailing global challenge in health care and requires the development of safe and efficient alternatives to classic antibiotics. Photodynamic Inactivation (PDI) has proven to be a promising alternative for treatment of a broad range of microorganisms. Photodynamic Inactivation uses photoactive molecules that generate reactive oxygen species (ROS) upon illumination and in the presence of oxygen, which immediately kill pathogenic target organisms. Relevant photoactive properties are provided by berberine. Originally extracted from Barberry (Berberis vulgaris), it is a natural compound widely used in Traditional Chinese Medicine for its antimicrobial and anti-inflammatory effects. With this study, we demonstrated the potential of berberine chloride hydrate (Ber) as a photosensitizer for PDI of important human pathogens, Gram(+) Staphylococcus capitis subsp. capitis, Gram(+) Staphylococcus aureus, and Gram(−) Escherichia coli. In vitro experiments on planktonic and biofilm cultures were conducted focusing on Ber activated with visible light in the blue wavelength range. The number of planktonic S. capitis cells was reduced by 7 log₁₀ steps using 100 µM Ber (5 min incubation, illumination with 435 nm LED array, radiant exposure 25 J/cm²). For an antibacterial effect of 4 log₁₀ steps, static S. capitis biofilms required 1 mM Ber, a drug-to-light interval of 60 min, and illumination with 100 J/cm². Almost all planktonic cells of Staphylococcus aureus could be photokilled using 100 µM Ber (drug-to-light interval of 30 min, radiant exposure 25 J/cm²). Biofilms of S. aureus could be phototreated (3 log₁₀ steps inactivation) when using 1 mM Ber incubated for 5 min and photoactivated with 100 J/cm². The study is highlighted by the proof that PDI treatment using Ber showed an antibacterial effect on Gram(−) E. coli. Planktonic cells could be reduced by 3 log₁₀ steps with 100 µM Ber (5 min incubation, 435 nm, 25 J/cm²). With 5 mM ethylenediamine tetraacetic acid disodium salt dihydrate (Na₂EDTA) or 1.2% polyaspartic acid (PASA) in addition, a relative inactivation of 4 log₁₀ steps and 7 log₁₀ steps, respectively, was detectable. Furthermore, we showed that an antibacterial effect of 3.4 log₁₀ towards E. coli biofilms was given when using 1 mM Ber (5 min incubation, 435 nm, 100 J/cm²). These results underscore the significance of PDI-treatment with Ber as a natural compound in combination with blue light as valuable antimicrobial application. Full article

Various studies have revealed that several cancer cell types can upregulate inducible nitric oxide synthase (iNOS) and iNOS-derived nitric oxide (NO) after moderate photodynamic treatment (PDT) sensitized by 5-aminolevulinic acid (ALA)-induced protoporphyrin-IX. As will be discussed, the NO signaled cell resistance to photokilling as well as greater growth and migratory aggressiveness of surviving cells. On this basis, it was predicted that diffusible NO from PDT-targeted cells in a tumor might enhance the growth, migration, and invasiveness of non- or poorly PDT-targeted bystander cells. This was tested using a novel approach in which ALA-PDT-targeted cancer cells on a culture dish were initially segregated from non-targeted bystander cells of the same type via impermeable silicone-rimmed rings. Several hours after LED irradiation, the rings were removed, and both cell populations were analyzed in the dark for various responses. After a moderate extent of targeted cell killing (~25%), bystander proliferation and migration were evaluated, and both were found to be significantly enhanced. Enhancement correlated with iNOS/NO upregulation in surviving PDT-targeted cancer cells in the following cell type order: PC3 > MDA-MB-231 > U87 > BLM. If occurring in an actual PDT-challenged tumor, such bystander effects might compromise treatment efficacy by stimulating tumor growth and/or metastatic dissemination. Mitigation of these and other negative NO effects using pharmacologic adjuvants that either inhibit iNOS transcription or enzymatic activity will be discussed. Full article

In this work, the preparation of inclusion complexes, (ICs) using magnesium phthalocyanine (MgPc) and various cyclodextrins (β-CD, γ-CD, HP-β-CD, Me-β-CD), using the kneading method is presented. Dynamic light scattering (DLS) indicated that the particles in dispersion possessed mean size values between 564 to 748 nm. The structural characterization of the ICs by infrared spectroscopy (FT-IR) and nuclear magnetic resonance (NMR) spectroscopy provides evidence of the formation of the ICs. The release study of the MgPc from the different complexes was conducted at pH 7.4 and 37 °C, and indicated that a rapid release (“burst effect”) of ~70% of the phthalocyanine occurred in the first 20 min. The kinetic model that best describes the release profile is the Korsmeyer–Peppas. The photodynamic therapy studies against the squamous carcinoma A431 cell line indicated a potent photosensitizing activity of MgPc (33% cell viability after irradiation for 3 min with 18 mW/cm²), while the ICs also presented significant activity. Among the different ICs, the γ-CD-MgPc IC exhibited the highest photokilling capacity under the same conditions (cell viability 26%). Finally, intracellular localization studies indicated the enhanced cellular uptake of MgPc after incubation of the cells with the γ-CD-MgPc complex for 4 h compared to MgPc in its free form. Full article

The main objective of this research is to determine the optimal application conditions of a newly synthesized multifunctional coating containing Ag-doped TiO₂ nanoparticles when used as a possible protective agent for sandstone. Firstly, Ag-TiO₂ nanoparticles with anatase structure, spherical shape and controllable sizes were prepared using the sol–gel method and characterized. The biocidal activity of Ag-doped TiO₂ NPs was studied by comparing its performance to pure TiO₂ NPs against two representative Gram-positive and Gram-negative bacterial strains, under both visible irradiation and in the dark; then, the antimicrobial efficiency of two different concentrations of Ag-TiO₂ nanoparticles (0.1–1 mol%) was evaluated against two phototrophic strains commonly isolated from deteriorated surfaces. Results showed that the photoactivation and photokilling activity of TiO₂ were highly improved by doping with Ag. Next, prepared nanopowders were dispersed in a binder with different powder/PDMS ratios: (0.1, 0.2, 0.5 and 1% w/v TiO₂) and then applied in different amounts (2, 3 and 6 g/m²) on Serena stone specimens. Results revealed that the application of 2 g/m² nanocomposite at powder/binder ratios equal to 1% w/v TiO₂ provided a fine hydrophobic character for the stone material with acceptable chromatic variations. Full article

The widespread diffusion of photodynamic therapy (PDT) as a clinical treatment for solid tumors is mainly limited by the patient’s adverse reaction (skin photosensivity), insufficient light penetration in deeply seated neoplastic lesions, unfavorable photosensitizers (PSs) biodistribution, and photokilling efficiency due to PS aggregation in biological environments. Despite this, recent preclinical studies reported on successful combinatorial regimes of PSs with chemotherapeutics obtained through the drugs encapsulation in multifunctional nanometric delivery systems. The aim of the present review deals with the punctual description of several nanosystems designed not only with the objective of co-transporting a PS and a chemodrug for combination therapy, but also with the goal of improving the therapeutic efficacy by facing the main critical issues of both therapies (side effects, scarce tumor oxygenation and light penetration, premature drug clearance, unspecific biodistribution, etc.). Therefore, particular attention is paid to the description of bio-responsive drugs and nanoparticles (NPs), targeted nanosystems, biomimetic approaches, and upconverting NPs, including analyzing the therapeutic efficacy of the proposed photo-chemotherapeutic regimens in in vitro and in vivo cancer models. Full article

A green method for depositing a CuO layer with good adhesion and a large surface area on a support of activated alumina (Al₂O₃) was evaluated. The relatively simple method consists of adsorption of a copper salt on the surface of Al₂O₃, formation of Cu(OH)₂, and subsequent decomposition of the hydroxide to CuO. The XRD confirmed that the deposited photocatalyst crystalized at low temperatures (80 °C). Furthermore, BET measurements show a surface area of about 90 m²/g. The large surface area is the result of the speed of the conversion and decomposition reactions. The photokilling properties of the prepared photocatalyst were evaluated using E. coli cells and the leaching of copper ions was determined using ICP-MS. The photocatalytic efficiency was also evaluated by the degradation of an organic azo dye. The prepared photocatalyst shows good activity in the purification and disinfection of treated water. The described method is economical, fast, and can be considered green, since the only byproducts are water and NaCl. Full article

Global crop production depends on strategies to counteract the ever-increasing spread of plant pathogens. Antibiotics are often used for large-scale treatments. As a result, Erwinia amylovora, causal agent of the contagious fire blight disease, has already evolved resistance to streptomycin (Sm). Photodynamic Inactivation (PDI) of microorganisms has been introduced as innovative method for plant protection. The aim of this study is to demonstrate that E. amylovora resistant to Sm (E. amylovora^SmR) can be killed by PDI. Two photosensitizers, the synthetic B17-0024, and the natural derived anionic sodium magnesium chlorophyllin (Chl) with cell-wall-permeabilizing agents are compared in terms of their photo-killing efficiency in liquid culture with or without 100 µg/mL Sm. In vitro experiments were performed at photosensitizer concentrations of 1, 10 or 100 µM and 5 or 30 min incubation in the dark, followed by illumination at 395 nm (radiant exposure 26.6 J/cm²). The highest inactivation of seven log steps was achieved at 100 µM B17-0024 after 30 min incubation. Shorter incubation (5 min), likely to represent field conditions, reduced the photo-killing to 5 log steps. Chlorophyllin at 100 µM in combination with 1.2% polyaspartic acid (PASA) reduced the number of bacteria by 6 log steps. While PASA itself caused some light independent toxicity, an antibacterial effect (3 log reduction) was achieved only in combination with Chl, even at concentrations as low as 10 µM. Addition of 100 µg/mL Sm to media did not significantly increase the efficacy of the photodynamic treatment. This study proves principle that PDI can be used to treat plant diseases even if causative bacteria are resistant to conventional treatment. Therefore, PDI based on natural photosensitizers might represent an eco-friendly treatment strategy especially in organic farming. Full article

In this work, metal-doped titanium dioxide (TiO₂) was synthesised with the aim of improving photocatalytic degradation and antimicrobial activities; TiO₂ was doped with copper (Cu) ranging from 0.1 to 1.0 wt%. The physical and chemical properties of the Cu-doped TiO₂ nanoparticles were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), the Brunauer–Emmett–Teller method (BET) and diffuse reflection spectroscopy (DRS). The results revealed that the anatase phase of TiO₂ was maintained well in all the Cu-doped TiO₂ samples. No significant difference in the particle sizes or the specific surface areas was caused by increasing Cu doping. However, the band gap decreased continuously from 3.20 eV for undoped TiO₂ to 3.12 eV for 1.0 wt.% Cu-doped TiO₂. In addition, the 0.1 wt.% Cu-doped TiO₂ displayed a much greater photocatalytic degradation of methylene blue (MB) and excellent antibacterial ability for Escherichia coli (E. coli) compared to undoped TiO₂. On the other hand, the high Cu doping levels had negative impacts on the surface charge of nanoparticles and charge transfer for OH• generation, resulting in decreasing MB degradation and E. coli photokilling for 1.0 wt.% Cu-doped TiO₂. Full article

The major limitation of any cancer therapy lies in the difficulty of precisely controlling the localization of the drug in the tumor cells. To improve this drawback, our study explores the use of actively-targeted chemo-photo-nanocarriers that recognize and bind to epidermal growth factor receptor-overexpressing cells and promote the local on-demand release of the chemotherapeutic agent doxorubicin triggered by light. Our results show that the attachment of high concentrations of doxorubicin to cetuximab-IRDye700DX-mesoporous silica nanoparticles yields efficient and selective photokilling of EGFR-expressing cells mainly through singlet oxygen-induced release of the doxorubicin from the nanocarrier and without any dark toxicity. Therefore, this novel triply functionalized nanosystem is an effective and safe nanodevice for light-triggered on-demand doxorubicin release. Full article

An endoscopic capsule is a miniaturized ingestible video camera used to acquire images of the gastrointestinal tract wirelessly. Being morphologically equivalent to any ingestible pill, they can be simply swallowed. Endoscopic capsules therefore present an inviting alternative to the traditional endoscope for the examination of the gastrointestinal tract as well for therapeutic purposes. Endoscopic capsules are considered a disruptive technology, as they have revolutionized the examination of the gastrointestinal tract in a relatively short time. The implementation of an active locomotion system can improve the performance of a capsule and, in the solution proposed in this paper, allows providing the capsule the needed power for therapeutic purposes. Alternative therapeutic solutions, based on optical solutions and capsule endoscopy can be applied to patients affected by Helicobacter pylori, a bacterium of the stomach that affects about half of the world population, mainly in developing countries. The infection can be asymptomatic or associated with slight symptomatology. In some cases, it can take to major pathologies or death. The literature reports results deriving from recent applications of photodynamic treatments to H. pylori. Specific wavelengths have been found to exhibit photo-killing capabilities toward the bacterium. Some solutions have been proposed based on the use of endoscopic devices and capsules capable of administering photodynamic therapy inside the stomach. The proposed treatments, however, are invasive and insufficient to achieve long-term eradication. In this work, the administration of photodynamic therapy is proposed, aimed at the eradication of H. pylori by means of an active endoscopic capsule with LED emission. The capsule design, in addition to the therapeutic module aimed at administering an appropriate light intensity at specific wavelengths already demonstrated in the literature, integrates an active locomotion system aimed at maximizing the efficiency of the treatment. Full article

Photocytotoxic activity sensitized by 5,10,15,20-tetrakis[4-(3-N,N-dimethylaminopropoxy)phenyl]chlorin (TAPC) was investigated in Candida albicans under different culture conditions. Planktonic cells incubated with 2.5 μM TAPC were eradicated after 5 min irradiation with white light. Studies in the presence of reactive oxygen species scavengers indicated the involvement of mainly a type II mechanism. Furthermore, cell growth of C. albicans was suppressed in the presence of 5 μM TAPC. A decrease in pseudohyphae survival of 5 log was found after 30 min irradiation. However, the photokilling of this virulence factor reached a 1.5 log reduction in human serum. The uptake of TAPC by pseudohyphae decreased in serum due to the interaction of TAPC with albumin. The binding constant of the TAPC-albumin complex was ~10⁴ M⁻¹, while the bimolecular quenching rate constant was ~10¹² s⁻¹ M⁻¹, indicating that this process occurred through a static process. Thus, the photoinactivation of C. albicans was considerably decreased in the presence of albumin. A reduction of 2 log in cell survival was observed using 4.5% albumin and 30 min irradiation. The results allow optimizing the best conditions to inactivate C. albicans under different culture conditions. Full article

Caries-related biofilms and associated complications are significant threats in dentistry, especially when biofilms grow over dental restorations. The inhibition of cariogenic biofilm associated with the onset of carious lesions is crucial for preventing disease recurrence after treatment. This in vitro study defined optimized parameters for using a photosensitizer, toluidine blue O (TBO), activated via a red light-emitting diode (LED)-based wireless device to control the growth of cariogenic biofilms. The effect of TBO concentrations (50, 100, 150, and 200 μg/mL) exposed to light or incubated in the dark was investigated in successive cytotoxicity assays. Then, a mature Streptococcus mutans biofilm model under sucrose challenge was treated with different TBO concentrations (50, 100, and 150 μg/mL), different light energy doses (36, 108, and 180 J/cm²), and different incubation times before irradiation (1, 3, and 5 min). The untreated biofilm, irradiation with no TBO, and TBO incubation with no activation represented the controls. After treatments, biofilms were analyzed via S. mutans colony-forming units (CFUs) and live/dead assay. The percentage of cell viability was within the normal range compared to the control when 50 and 100 μg/mL of TBO were used. Increasing the TBO concentration and energy dose was associated with biofilm inhibition (p < 0.001), while increasing incubation time did not contribute to bacterial elimination (p > 0.05). Irradiating the S. mutans biofilm via 100 μg/mL of TBO and ≈180 J/cm² energy dose resulted in ≈3-log reduction and a higher amount of dead/compromised S. mutans colonies in live/dead assay compared to the control (p < 0.001). The light energy dose and TBO concentration optimized the bacterial elimination of S. mutans biofilms. These results provide a perspective on the determining parameters for highly effective photo-killing of caries-related biofilms and display the limitations imposed by the toxicity of the antibacterial photodynamic therapy’s chemical components. Future studies should support investigations on new approaches to improve or overcome the constraints of opportunities offered by photodynamic inactivation of caries-related biofilms. Full article

Magnesium(II) tribenzoporphyrazines with phenoxybutylsulfanyl substituents were evaluated as photosensitizers in terms of their optical properties against wound bacteria. In the UV-vis spectra of analyzed tribenzoporphyrazines, typical absorption ranges were found. However, the emission properties were very weak, with fluorescence quantum yields in the range of only 0.002–0.051. What is important, they revealed moderate abilities to form singlet oxygen with the quantum yields up to 0.27. Under irradiation, the macrocycles decomposed via photobleaching mechanism with the quantum yields up to 8.64 × 10⁻⁵. The photokilling potential of tribenzoporphyrazines was assessed against Streptococcus pyogenes, Staphylococcus epidermidis, as well as various strains of Staphylococcus aureus, including methicillin-sensitive and-resistant bacteria. Both evaluated photosensitizers revealed high photodynamic potential against studied bacteria (>3 logs). S.aureus growth was reduced by over 5.9 log, methicillin-resistant S. aureus by 5.1 log, S.epidermidis by over 5.7 log, and S. pyogenes by over 4.7 log. Full article

This work aims to enhance the photocatalytic antibacterial performance of plastics according to the JIS Z 2801:2010 standard, and to determine their mechanical properties by studying: (i) the influence of calcination on titanium dioxide (TiO₂); (ii) modification with different TiO₂ concentrations, and; (iii) the effect of silane as a coupling agent. Acrylonitrile-butadiene-styrene plastics (ABS) and Escherichia coli (E. coli) were chosen as the model plastic and bacteria, respectively. The 500 °C calcined TiO₂ successfully provided the best photoantibacterial activity, with an approximately 62% decrease of E. coli colony counts following 30 min of exposure. Heat treatment improved the crystallinity of anatase TiO₂, resulting in low electron-hole recombination, while effectively adsorbing reactants on the surface. ABS with 500 °C-calcined TiO₂ at the concentration of 1 wt % gave rise to the highest performance due to the improved distribution of TiO₂. At this point, blending silane coupling agent could further improve the efficacy of photoantibacterial activity up to 75% due to greater interactions with the polymer matrix. Moreover, it could promote a 1.6-fold increase of yield strength via increased adherent bonding between TiO₂ and the ABS matrix. Excellent photocatalytic and material stability can be achieved, with constant photocatalytic efficiency remaining for up to five reuse cycles without loss in the yield strength. Full article

Drug-resistant bacteria threaten the health of people world-wide and cause high costs to their health systems. According to Scientific American, the number of regrettable fatalities due to the bacteria that are resistant to conventional antibiotics will sum up to 300 million until 2050 if the problem is not tackled immediately. Photodynamic Inactivation (PDI) has proven effective against microorganisms irrespective of their resistance to conventional treatment, but for the translation into clinical practice, economic, homogenous and powerful light sources holding approval as medical devices are needed. In this study we present two novel light emitting diode (LED)-based lamps (Repuls7PDI-red and Repuls7PDI-blue) tailored for application in PDI and demonstrate their photodynamic efficiency upon using either methylene blue (MB), a photoactive compound widely used in PDI, or Sodium Magnesium Chlorophyllin (CHL), a water-soluble derivative of chlorophyll, which holds approval as food additive E140, against bacteria and fungi. Gram+ Staphylococcus aureus, Gram− Escherichia coli and the yeast Candida albicans serve as model systems. Repuls7PDI-red emits a wavelength of 635 nm and an intensity of 27.6 ± 2.4 mW·cm⁻² at a distance of 13.5 cm between the light source and the target, while the Repuls7PDI-blue allows an exposure at 433 nm (within the range of violet light) (6.4 ± 0.5 mW·cm⁻² at 13.5 cm). Methylene blue was photoactivated with the Repuls7PDI-red at 635 nm (25.6 J·cm⁻²) and allows for photokilling of E. coli by more than 6 log₁₀ steps at a concentration of 10 µM MB. Using equal parameters, more than 99.99999% of S. aureus (20 µM MB) and 99.99% of C. albicans (50 µM MB) were killed. If blue light (Repuls7PDI-blue, 433 nm, 6.6 J·cm²) is used to trigger the production of reactive oxygen species (ROS), a photoinactivation of S. aureus (5 µM CHL, CFU reduction > 7 log₁₀) and C. albicans (>7 log₁₀) below the detection limit is achieved. PDI based on CHL (10 µM) using red light activation reduces the number of viable S. aureus by more than 6 log₁₀. Our data prove that both LED-based light sources are applicable for Photodynamic Inactivation. Their easy-to-use concept, high light output and well-defined wavelength might facilitate the translation of PDI into clinical practice. Full article