Blue-Light-Activated Water-Soluble Sn(IV)-Porphyrins for Antibacterial Photodynamic Therapy (aPDT) against Drug-Resistant Bacterial Pathogens.

Antimicrobial resistance has emerged as a global threat to the treatment of infectious diseases. Antibacterial photodynamic therapy (aPDT) is a promising alternative approach and is highly suitable for the treatment of cutaneous bacterial infections through topical applications. aPDT relies on light-responsive compounds called photosensitizer (PS) dyes, which generate reactive oxygen species (ROS) when induced by light, thereby killing bacterial cells. Despite several previous studies in this area, the molecular details of targeting and cell death mediated by PS dyes are poorly understood. In this study, we further investigate the antibacterial properties of two water-soluble Sn(IV) tetrapyridylporphyrins that were quaternized with methyl and hexyl groups (1 and 2). In this follow-up study, we demonstrate that Sn(IV)-porphyrins can be photoexcited by blue light (a 427 nm LED) and exhibit various levels of bactericidal activity against both Gram-(+) and Gram-(-) strains of bacteria. Using localization studies through fluorescence microscopy, we show that 2 targets the bacterial membrane more effectively than 1 and exhibits comparatively higher aPDT activity. Using multiple fluorescence reporters, we demonstrate that photoactivation of 1 and 2 results in extensive collateral damage to the bacterial cells including DNA cleavage, membrane damage, and delocalization of central systems necessary for bacterial growth and division. In summary, this investigation provides deep insights into the mechanism of bacterial killing mediated by the Sn(IV)-porphyrins. Moreover, our approach offers a new method for evaluating the activity of PS, which may inspire the discovery of new PS with enhanced aPDT activity.

Stress response in Escherichia coli following sublethal phenalene-1-one mediated antimicrobial photodynamic therapy: an RNA-Seq study.

Since the molecular mechanisms behind adaptation and the bacterial stress response toward antimicrobial photodynamic therapy (aPDT) are not entirely clear yet, the aim of the present study was to investigate the transcriptomic stress response in Escherichia coli after sublethal treatment with aPDT using RNA sequencing (RNA-Seq). Planktonic cultures of stationary phase E. coli were treated with aPDT using a sublethal dose of the photosensitizer SAPYR. After treatment, RNA was extracted, and RNA-Seq was performed on the Illumina NextSeq 500. Differentially expressed genes were analyzed and validated by qRT-PCR. Furthermore, expression of specific stress response proteins was investigated using Western blot analysis.The analysis of the differential gene expression following pathway enrichment analysis revealed a considerable number of genes and pathways significantly up- or down-regulated in E. coli after sublethal treatment with aPDT. Expression of 1018 genes was up-regulated and of 648 genes was down-regulated after sublethal treatment with aPDT as compared to irradiated controls. Analysis of differentially expressed genes and significantly de-regulated pathways showed regulation of genes involved in oxidative stress response and bacterial membrane damage. In conclusion, the results show a transcriptomic stress response in E. coli upon exposure to aPDT using SAPYR and give an insight into potential molecular mechanisms that may result in development of adaptation.

Optimal effective concentration combinations (OPECCs) for binary application of membrane-targeting antiseptics and TMPyP-mediated antimicrobial photodynamic therapy.

The widespread occurrence of multi-resistant bacteria is a health problem of global dimension. Infections caused by multi-resistant pathogens are difficult to treat and often associated with high mortality. Therefore, new treatment strategies are of interest, such as the use of differently acting antibacterial concepts. One of these new concepts is the use of antiseptics in combination with the antibacterial photodynamic therapy (aPDT). Currently, no method has yet been established as a standard procedure for investigating combined effects and evaluating them in a generally valid and unambiguous manner. The focus of this study was on how cationic antiseptics benzalkonium chloride (BAC) and chlorhexidine digluconate (CHX) behave in a combined application with aPDT using the photosensitizer TMPyP. For this purpose, BAC and CHX were applied in combination with the aPDT using TMPyP in non-lethal concentrations to the three bacteria Escherichia coli, Staphylococcus aureus, and Enterococcus faecalis. The results of the combination experiments with sublethal concentrations of BAC or CHX with the aPDT showed that the binary application had a lethal effect. Irrespective of the bacteria, the reduction in concentrations in OPECC, compared to individual concentrations, was more than 50% for TMPyP, 23-40% for BAC, and 18-43% for CHX. Furthermore, the optimal effective concentration combinations (OPECCs) could be determined. The latter showed that the combined application allowed the reduction of both concentrations compared to the single application.

In vitro study: methylene blue-based antibacterial photodynamic inactivation of Pseudomonas aeruginosa.

Pseudomonas aeruginosa is one of the most antibiotic-resistant and opportunistic pathogens in immunocompromised and debilitated patients. It is considered the cause of most severe skin infections and is frequently found in hospital burn units. Due to its high antibiotic resistance, eliminating P. aeruginosa from skin infections is quite challenging. Therefore, this study aims to assess the novel in vitro antibacterial activity of methylene blue using a 635-nm diode laser to determine the effective power and energy densities for inhibition of P. aeruginosa. The strain was treated with various concentrations of methylene blue and 635-nm diode laser at powers of 300 mW/cm2 and 250 mW/cm2. The diode laser's potency in the photo-destruction of methylene blue and its degradation through P. aeruginosa were also evaluated. Colony-forming unit (CFU)/ml, fluorescence spectroscopy, optical density, and confocal microscopy were used to measure the bacterial killing effect. As a result, the significant decrease of P. aeruginosa was 2.15-log10, 2.71-log10, and 3.48-log10 at 60, 75, and 90 J/cm2 after excitation of MB for 240, 300, and 360 s at a power of 250 mW/cm2, respectively. However, a maximum decrease in CFU was observed by 2.54-log10 at 72 J/cm2 and 4.32-log10 at 90 and 108 J/cm2 after 300 mW/cm2 of irradiation. Fluorescence images confirmed the elimination of bacteria and showed a high degree of photo-destruction compared to treatment with methylene blue and light alone. In conclusion, MB-induced aPDT demonstrated high efficacy, which could be a potential approach against drug-resistant pathogenic bacteria. KEY POINTS: • Combination of methylene blue with 635-nm diode laser for antibacterial activity. • Methylene blue photosensitizer is employed as an alternative to antibiotics. • aPDT showed promising antibacterial activity against Pseudomonas aeruginosa.

Effectiveness of antimicrobial photodynamic therapy in the treatment of peri-implantitis: systematic review and meta-analysis.

The purpose of this study was to evaluate the current scientific evidence on the effectiveness of antimicrobial photodynamic therapy (aPDT) as an adjunctive treatment to mechanical debridement in the treatment of peri-implantitis. The Preferred Reporting Items for Systematic Reviews and Meta-analyses was followed. A protocol was registered in the International Prospective Registry of Systematic Reviews (PROSPERO #CRD42022361684). The search was carried out in seven databases, with no restrictions regarding language or year of publication. Our work included studies that compared clinical periodontal parameters between individuals treated with mechanical debridement associated with aPDT and a control group of patients who had undergone mechanical debridement alone. Study selection, data extraction, and risk of bias assessment (RoB 2.0) were performed by two review authors. Meta-analysis was performed. The mean difference (MD) and a 95% confidence interval (CI) were provided. Four hundred and seven-four studies were identified, of which five studies were included. The meta-analysis demonstrated that aPDT adjunctive to mechanical debridement in subjects with peri-implantitis resulted in greater reduction in probing depth 3 months after treatment than among subjects receiving treatment with mechanical debridement. Most of the included studies exhibit a low risk of bias. Adjunctive aPDT to mechanical debridement contributes to the improvement of peri-implant clinical parameters in individuals with peri-implantitis, in particular probing depth.

Effectiveness of laser pulsed irradiation for antimicrobial photodynamic therapy.

The aim of this study was to compare two types of light irradiation devices for antimicrobial photodynamic therapy (aPDT). A 660-nm light-emitting diode (LED) and a 665-nm laser diode (LD) were used for light irradiation, and 0.1 mg/L TONS 504, a cationic chlorin derivative, was used as the photosensitizer. We evaluated the light attenuation along the vertical and horizontal directions, temperature rise following light irradiation, and aPDT efficacy against Staphylococcus aureus under different conditions: TONS 504 only, light irradiation only, and TONS 504 with either LED (30 J/cm2) or LD light irradiation (continuous: 30 J/cm2; pulsed: 20 J/cm2 at 2/3 duty cycle, 10 J/cm2 at 1/3 duty cycle). Both LED and LD light intensities were inversely proportional to the square of the vertical distance from the irradiated area. Along the horizontal distance from the nadir of the light source, the LED light intensity attenuated according to the cosine quadrature law, while the LD light intensity did not attenuate within the measurable range. Following light irradiation, the temperature rise increased as the TONS 504 concentration increased in the order of pulsed LD < continuous LD < LED irradiation. aPDT with light irradiation only or TONS 504 only had no antimicrobial effect, while aPDT with TONS 504 under continuous or pulsed LD light irradiation provided approximately 3 log reduction at 30 J/cm2 and 20 J/cm2 and approximately 2 log reduction at 10 J/cm2. TONS 504-aPDT under pulsed LD light irradiation provided anti-microbial effect without significant temperature rise.

Comparative Transcriptome Analysis of T. rubrum, T. mentagrophytes, and M. gypseum Dermatophyte Biofilms in Response to Photodynamic Therapy.

Dermatophyte biofilms frequently count for inadequate responses and resistance to standard antifungal treatments, resulting in refractory chronic onychomycosis infection. Although antimicrobial photodynamic therapy (aPDT) has clinically proven to exert significant antifungal effects or even capable of eradicating dermatophyte biofilms, considerably less is known about the molecular mechanisms underlying aPDT and the potential dysregulation of signaling networks that could antagonize its action. The aim of this study is to elucidate the molecular mechanisms underlining aPDT combat against dermatophyte biofilm in recalcitrant onychomycosis and to decipher the potential detoxification processes elicited by aPDT, facilitating the development of more effective photodynamic interventions. We applied genome-wide comparative transcriptome analysis to investigate how aPDT disrupting onychomycosis biofilm formed by three distinct dermatophytes, including Trichophyton rubrum, Trichophyton mentagrophytes, and Microsporum gypseum, the most frequently occurring pathogenic species. In total, 352.13 Gb of clean data were obtained for the transcriptomes of dermatophyte biofilms with or without aPDT treatment, resulting in 2,422.42 million reads with GC content of 51.84%, covering 99.9%, 98.5% and 99.4% of annotated genes of T. rubrum, T. mentagrophytes, and M. gypseum, respectively. The genome-wide orthologous analysis identified 6624 transcribed single-copy orthologous genes in all three species, and 36.5%, 6.8% and 17.9% of which were differentially expressed following aPDT treatment. Integrative orthology analysis demonstrated the upregulation of oxidoreductase activities is a highly conserved detoxification signaling alteration in response to aPDT across all investigated dermatophyte biofilms. This study provided new insights into the molecular mechanisms underneath anti-dermatophyte biofilm effects of aPDT and successfully identified a conserved detoxification regulation upon the aPDT application.

Efficacy of Curcumin-Mediated Antimicrobial Photodynamic Therapy on Candida spp.-A Systematic Review.

Oral candidiasis is a common problem among immunocompetent patients. The frequent resistance of Candida strains to popular antimycotics makes it necessary to look for alternative methods of treatment. The authors conducted a systematic review following the PRISMA 2020 guidelines. The objective of this review was to determine if curcumin-mediated blue light could be considered as an alternative treatment for oral candidiasis. PubMed, Google Scholar, and Cochrane Library databases were searched using a combination of the following keywords: (Candida OR candidiasis oral OR candidiasis oral OR denture stomatitis) AND (curcumin OR photodynamic therapy OR apt OR photodynamic antimicrobial chemotherapy OR PACT OR photodynamic inactivation OR PDI). The review included in vitro laboratory studies with Candida spp., in vivo animal studies, and randomized control trials (RCTs) involving patients with oral candidiasis or prosthetic stomatitis, published only in English. The method of elimination of Candida species in the studies was curcumin-mediated aPDT. A total of 757 studies were identified. Following the analysis of the titles and abstracts of the studies, only 42 studies were selected for in-depth screening, after which 26 were included in this study. All studies evaluated the antifungal efficacy of curcumin-mediated aPDT against C. albicans and non-albicans Candida. In studies conducted with planktonic cells solutions, seven studies demonstrated complete elimination of Candida spp. cells. The remaining studies demonstrated only partial elimination. In all cases, experiments on single-species yeast biofilms demonstrated partial, statistically significant inhibition of cell growth and reduction in biofilm mass. In vivo, curcumin-mediated aPDT has shown good antifungal activity against oral candidiasis also in an animal model. However, its clinical efficacy as a potent therapeutic strategy for oral candidiasis requires few further RCTs.

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.

Antimicrobial Photodynamic Therapy in the Nasal Decolonization of Maintenance Hemodialysis Patients: A Pilot Randomized Trial.

RATIONALE & OBJECTIVE: Infections are an important cause of mortality among patients receiving maintenance hemodialysis. Staphylococcus aureus is a frequent etiological agent, and previous nasal colonization is a risk factor for infection. Repeated antimicrobial decolonization reduces infection in this population but can induce antibiotic resistance. We compared photodynamic therapy, a promising bactericidal treatment that does not induce resistance, to mupirocin treatment among nasal carriers of S aureus. STUDY DESIGN: Randomized controlled pilot study. SETTING & PARTICIPANTS: 34 patients receiving maintenance hemodialysis who had nasal carriage of S aureus. INTERVENTIONS: Patients were randomly assigned to decolonization with a single application of photodynamic therapy (wavelength of 660nm, 400mW/cm2, 300 seconds, methylene blue 0.01%) or with a topical mupirocin regimen (twice a day for 5 days). OUTCOME: Nasal swabs were collected at time 0 (when the carrier state was identified), directly after treatment completion, 1 month after treatment, and 3 months after treatment. Bacterial isolates were subjected to proteomic analysis to identify the species present, and antimicrobial susceptibility was characterized. RESULTS: All 17 participants randomized to photodynamic therapy and 13 of 17 (77%) randomized to mupirocin were adherent to treatment. Directly after treatment was completed, 12 participants receiving photodynamic therapy (71%) and 13 participants treated with mupirocin (77%) had cultures that were negative for S aureus (risk ratio, 0.92 [95% CI, 0.61-1.38]; P=0.9). Of the patients who had negative cultures directly after completion of photodynamic therapy, 67% were recolonized within 3 months. There were no adverse events in the photodynamic therapy group. LIMITATIONS: Testing was restricted to assessing nasal colonization; infectious complications were not assessed. CONCLUSIONS: Photodynamic therapy is a feasible approach to treating nasal carriage of S aureus. Future larger studies should be conducted to determine whether photodynamic therapy is equivalent to the standard of care with mupirocin. FUNDING: Government grant (National Council for Scientific and Technological Development process 3146682020-9). TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT04047914.

On the Photo-Eradication of Methicillin-Resistant Staphylococcus aureus Biofilm Using Methylene Blue.

This work compared the effectiveness of several Methylene Blue (MB)-based protocols for photo-eradication of biofilms formed on the surface of the glass and stainless steel discs by S. aureus MRSA isolates using a diode laser (λ = 665 nm; output power 40 mW; energy fluence was 189 J cm-2). The results obtained showed that MB alone, up to a concentration of 62.5 mgL-1, had limited photo-bactericidal activity. It was possible to enhance the activity of MB using two types of spherical gold nanoparticles of similar sizes, 15 ± 3 nm/20 ± 3 nm, but differing in the method of their synthesis and stabilization. The enhancement of the photodestruction effect was related to the increased production of hydroxyl radicals by the MB+gold nanoparticles mixture, and this mixture showed dark cytotoxicity against the cocci studied. Effective destruction (mortality above 99.9%) of the biofilms formed by MRSA isolates was also possible without the use of gold nanoparticles, but the concentration of MB had to be at least 125 mgL-1. A highly efficient protocol of photodestruction of biofilms, consisting of triple exposure of biofilms to laser light in the presence of MB alone, combined with the removal of dead bacteria protecting deep layers of pathogens against photosensitization, was also described.

Inherently Antimicrobial P(MMA-ran-DMAEMA) Copolymers Sensitive to Photodynamic Therapy: A Double Bactericidal Effect for Active Wound Dressing.

In this work, two compounds belonging to the BODIPY family, and previously investigated for their photosensitizing properties, have been bound to the amino-pendant groups of three random copolymers, with different amounts of methyl methacrylate (MMA) and 2-(dimethylamino)ethyl methacrylate (DMAEMA) in the backbone. The P(MMA-ran-DMAEMA) copolymers have inherently bactericidal activity, due to the amino groups of DMAEMA and to the quaternized nitrogens bounded to BODIPY. Systems consisting of filter paper discs coated with copolymers conjugated to BODIPY were tested on two model microorganisms, Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). On solid medium, irradiation with green light induced an antimicrobial effect, visible as a clear inhibition area around the coated disks. The system based on the copolymer with 43% DMAEMA and circa 0.70 wt/wt% of BODIPY was the most efficient in both bacterial species, and a selectivity for the Gram-positive model was observed, independently of the conjugated BODIPY. A residual antimicrobial activity was also observed after dark incubation, attributed to the inherently bactericidal properties of copolymers.

In Vitro Photoinactivation of Fusarium oxysporum Conidia with Light-Activated Ammonium Phthalocyanines.

Antimicrobial photodynamic therapy (aPDT) has been explored as an innovative therapeutic approach because it can be used to inactivate a variety of microbial forms (vegetative forms and spores) without causing significant damage to host tissues, and without the development of resistance to the photosensitization process. This study assesses the photodynamic antifungal/sporicidal activity of tetra- and octasubstituted phthalocyanine (Pc) dyes with ammonium groups. Tetra- and octasubstituted zinc(II) phthalocyanines (1 and 2) were prepared and tested as photosensitizers (PSs) on Fusarium oxysporum conidia. Photoinactivation (PDI) tests were conducted with photosensitizer (PS) concentrations of 20, 40, and 60 µM under white-light exposure at an irradiance of 135 mW·cm-2, applied during 30 and 60 min (light doses of 243 and 486 J·cm-2). High PDI efficiency corresponding to the inactivation process until the detection limit was observed for both PSs. The tetrasubstituted PS was the most effective, requiring the lowest concentration and the shortest irradiation time for the complete inactivation of conidia (40 µM, 30 min, 243 J·cm-2). Complete inactivation was also achieved with PS 2, but a longer irradiation time and a higher concentration (60 µM, 60 min, 486 J·cm-2) were necessary. Because of the low concentrations and moderate energy doses required to inactivate resistant biological forms such as fungal conidia, these phthalocyanines can be considered potent antifungal photodynamic drugs.

Ruthenium(II)-Arene Curcuminoid Complexes as Photosensitizer Agents for Antineoplastic and Antimicrobial Photodynamic Therapy: In Vitro and In Vivo Insights.

Photodynamic therapy (PDT) is an anticancer/antibacterial strategy in which photosensitizers (PSs), light, and molecular oxygen generate reactive oxygen species and induce cell death. PDT presents greater selectivity towards tumor cells than conventional chemotherapy; however, PSs have limitations that have prompted the search for new molecules featuring more favorable chemical-physical characteristics. Curcumin and its derivatives have been used in PDT. However, low water solubility, rapid metabolism, interference with other drugs, and low stability limit curcumin use. Chemical modifications have been proposed to improve curcumin activity, and metal-based PSs, especially ruthenium(II) complexes, have attracted considerable attention. This study aimed to characterize six Ru(II)-arene curcuminoids for anticancer and/or antibacterial PDT. The hydrophilicity, photodegradation rates, and singlet oxygen generation of the compounds were evaluated. The photodynamic effects on human colorectal cancer cell lines were also assessed, along with the ability of the compounds to induce ROS production, apoptotic, necrotic, and/or autophagic cell death. Overall, our encouraging results indicate that the Ru(II)-arene curcuminoid derivatives are worthy of further investigation and could represent an interesting option for cancer PDT. Additionally, the lack of significant in vivo toxicity on the larvae of Galleria mellonella is an important finding. Finally, the photoantimicrobial activity of HCurc I against Gram-positive bacteria is indeed promising.

Photoantibacterial Poly(vinyl)chloride Films Applying Curcumin Derivatives as Bio-Based Plasticizers and Photosensitizers.

Herein we describe the design of natural curcumin ester and ether derivatives and their application as potential bioplasticizers, to prepare photosensitive phthalate-free PVC-based materials. The preparation of PVC-based films incorporating several loadings of newly synthesized curcumin derivatives along with their standard solid-state characterization is also described. Remarkably, the plasticizing effect of the curcumin derivatives in the PVC material was found to be similar to that observed in previous PVC-phthalate materials. Finally, studies applying these new materials in the photoinactivation of S. aureus planktonic cultures revealed a strong structure/activity correlation, with the photosensitive materials reaching up to 6 log CFU reduction at low irradiation intensities.

Rational approaches towards inorganic and organometallic antibacterials.

The occurrence of drug-resistant bacteria is drastically rising and new and effective antibiotic classes are urgently needed. However, most of the compounds in development are minor modifications of previously used drugs to which bacteria can easily develop resistance. The investigation of inorganic and organometallic compounds as antibiotics is an alternative approach that holds great promises due to the ability of such molecules to trigger metal-specific mechanisms of action, which results in lethal consequences for pathogens. In this review, a selection of concepts to rationally design inorganic and organometallic antibiotics is discussed, highlighting their advantages by comparing them to classical drug discovery programmes. The review concludes with a short perspective for the future of antibiotic drug development and the role metal-based compounds will play in the field.

Recent advances in nanoparticle-based targeting tactics for antibacterial photodynamic therapy.

The rise of antibacterial drug resistance means treatment options are becoming increasingly limited. We must find ways to tackle these hard-to-treat drug-resistant and biofilm infections. With the lack of new antibacterial drugs (such as antibiotics) reaching the clinics, research has switched focus to exploring alternative strategies. One such strategy is antibacterial photodynamic therapy (aPDT), a system that relies on light, oxygen, and a non-toxic dye (photosensitiser) to generate cytotoxic reactive oxygen species. This technique has already been shown capable of handling both drug-resistant and biofilm infections but has limited clinical approval to date, which is in part due to the low bioavailability and selectivity of hydrophobic photosensitisers. Nanotechnology-based techniques have the potential to address the limitations of current aPDT, as already well-documented in anti-cancer PDT. Here, we review recent advances in nanoparticle-based targeting tactics for aPDT.

Use of photodynamic therapy and photobiomodulation as alternatives for microbial control on clinical and subclinical mastitis in sheep.

Evaluate the effects of antimicrobial photodynamic therapy (aPDT) and photobiomodulation (PBM) as alternatives in the treatment of mastitis in sheep. A total of 100 sheep were evaluated, and four teats with clinical mastitis and 16 teats with subclinical mastitis were selected. Milk was collected for isolation and identification of microorganisms. They were grown on TSA, EMB, and MacConkey agar for 24 h, and the microorganisms were identified by Gram stain and biochemical tests. The ceilings were subdivided into four groups: G1, treatment with photosensitizer; G2, treatment with PBM (diode laser λ = 660 nm); G3, aPDT with methylene blue, and G4, control group. Milk samples were collected before, 24 and 48 h after treatments. Cases of subclinical mastitis presented coagulase-negative Staphylococcus and Streptococcus spp, and clinical mastitis had Escherichia coli grow from the samples. The treatments decrease the total bacterial count of negative coagulase Staphylococcus, Streptococcus spp, and Escherichia coli. Comparing the treatments, aPDT stood out, as it was able to photoinactivate all bacteria. Treatment with methylene blue photosensitizer, PBM, and aPDT induced the initial microbial reduction, but aPDT was more effective 48 h after treatment.

The benefit of antimicrobial photodynamic therapy to mechanical debridement in the treatment of smokers with peri-implant diseases: a systematic review and meta-analysis.

Antimicrobial photodynamic therapy (aPDT) has been proposed as an adjunctive treatment strategy for peri-implant diseases. This systematic review aimed to determine whether aPDT as an adjunct to mechanical debridement has an additional benefit for smokers with peri-implant diseases. Randomized controlled trials (RCTs), which evaluated the clinical outcomes of mechanical debridement alone versus mechanical debridement + aPDT among smokers, were considered eligible to be included. The primary outcome was bleeding on probing (BOP) and secondary outcomes included probing depth (PD), plaque index (PI), and crestal bone loss (CBL). Meta-analyses using a random-effects model were conducted to calculate the mean difference (MD) with a 95% confidence interval (CI). The quality of evidence was assessed according to Grading of Recommendations Assessment, Development and Evaluation (GRADE). A total of four RCTs (188 participants) were included. The aPDT group showed significantly improved PD (MD = - 1.26, 95% CI = - 2.19 to - 0.32, p = 0.008) and PI (MD = - 10.6%, 95% CI = - 14.46 to - 6.74%, p = 0.0001) compared with mechanical debridement group at 3-month follow-up. No significant difference in bleeding on probing (BOP) was observed at 3-month follow-up (MD = - 0.60%, 95% CI = - 2.36 to 1.16%, p = 0.50). The subgroup analyses on photosensitizers demonstrated significant differences between the two groups on PD (MD = - 1.23, 95% CI = - 2.41 to - 0.05, p = 0.04) and PI (MD = - 12.33, 95% CI = - 14.74 to - 9.92, p < 0.00001) by the use of methylene blue (MB). Within the limitation of this study, compared with mechanical debridement alone, combined use of aPDT was more effective in reducing PD and PI in smokers at 3-month follow-up. MB was a predictable photosensitizer for aPDT. However, the findings should be interpreted with caution due to the limited number of included studies, methodological deficiencies, and heterogeneity between studies.

Antibacterial Efficacy and Mechanisms of Curcumin-Based Photodynamic Treatment against Staphylococcus aureus and Its Application in Juices.

Antimicrobial Photodynamic Treatment (aPDT) is a non-thermal sterilization technology, which can inactivate common foodborne pathogens. In the present study, photodynamic inactivation on Staphylococcus aureus (S. aureus) with different concentrations of curcumin and light dose was evaluated and the mechanisms were also investigated. The results showed that curcumin-based aPDT could inactivate S. aureus cells by 6.9 log CFU/mL in phosphate buffered saline (PBS). Moreover, the modified Gompertz model presented a good fit at the inactivation data of S. aureus. Photodynamic treatment caused cell membrane damage as revealed by analyzing scanning electron microscopy (SEM) images. Leakage of intracellular constituents further indicated that cell membrane permeability was changed. Flow cytometry with double staining demonstrated that cell membrane integrity and the activity of nonspecific esterase were destroyed. Compared with the control group, intracellular reactive oxygen species (ROS) levels caused by photodynamic treatment significantly increased. Furthermore, curcumin-based aPDT reduced S. aureus by 5 log CFU/mL in juices. The color of the juices was also tested using a Chromatic meter, and it was found that b* values were the most markedly influenced by photodynamic treatment. Overall, curcumin-based aPDT had strong antibacterial activity against S. aureus. This approach has the potential to remove foodborne pathogens from liquid food.