Antimicrobial Photodynamic Therapy Research Articles

Low-intensity laser-assisted antimicrobial photodynamic therapy and intravascular laser irradiation of blood in oncology: systematic review and a brief report

Low-intensity laser-assisted antimicrobial photodynamic therapy and intravascular laser irradiation of blood in oncology: systematic review and a brief report

Effect of Antimicrobial Photodynamic Therapy on the Tongue Dorsum on Reducing Halitosis and the Duration of the Effect: A Randomized Clinical Trial

Antimicrobial photodynamic therapy (PDT) is a treatment that is gaining popularity in modern clinical medicine. However, little is known about the effect of PDT alone on reducing oral halitosis and the duration of the effect. This trial examined the effect of PDT on the tongue dorsum on reducing oral halitosis and the duration of the effect. This study was approved by the Ethics Committee of Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, and Okayama University Hospital (CRB20-015), and it was registered in the Japan Registry of Clinical Trials (jRCTs061200060). Twenty-two participants were randomly assigned to two groups: an intervention group and control group. PDT was performed in the intervention group using red laser emission and methylene blue gel on the middle and posterior area of the tongue dorsum. The concentration of volatile sulfur compounds, bacterial count on the tongue dorsum, probing pocket depth, bleeding on probing, and simplified oral debris index score were determined before and 1 week after PDT. The Mann–Whitney U test was used to assess the significance of the differences in each parameter between the two groups. We found that the hydrogen sulfide concentration and bacterial count on the tongue dorsum were decreased in the intervention group, but there was no statistically significant difference between the two groups. These results indicated that performing only PDT on the tongue dorsum may not contribute to reducing halitosis.

Successful Intentional Replantation of a Severely Compromised Tooth Using 3 Types of Phototherapy: A Case Report.

Background: Intentional replantation (IR) is an emerging and cost-effective last-resort treatment for persistent apical periodontitis. Adjunctive phototherapy for IR aims to improve the management of challenging cases by enhancing disinfection, stimulating healing and promoting regeneration. Objective: We report a novel phototherapy-assisted IR protocol conducted on a compromised lateral incisor with an extensive periapical infection (Ø > 10 mm) in a 68-year-old diabetic male. Methods: The IR protocol involved pre- and postoperative photobiomodulation (660 nm, 0.2 J/cm2, 60 sec/site), antimicrobial photodynamic therapy of the root surface (660 nm, 0.6 J/cm2, 30 sec, methylene blue photosensitizer), and Er:YAG root and socket debridement (2940 nm, 21 J/cm2, 30 sec). The total time from extraction to replantation was 14 min 35 sec. Results: The tooth at 3.5-year follow-up remained clinically functional with radiographic resolution of the infection indicating a successful reimplantation. Conclusions: This case report demonstrated that an adjunctive phototherapy IR protocol can effectively treat a compromised tooth with extensive periapical infection.

Biological Performance of Hexadeca-Substituted Metal Phthalocyanine/Reduced Graphene Oxide Nanobioagents.

This study presents a tetra-substituted phthalonitrile derivative, namely, diethyl 2-(3,4-dicyano-2,5-bis(hexyloxy)-6-(4-(trifluoromethoxy)phenoxy)phenyl)malonate (a), cyclotetramerizing in the presence of some metal salts. The resultant hexadeca-substituted metal phthalocyanines [M= Co, Zn, InCl)] (b-d) were used for the modification of reduced graphene oxide for the first time. The effect of the phthalonitrile/metal phthalocyanines on biological features of reduced graphene oxide (rGO) was extensively examined by the investigation of antioxidant, antimicrobial, DNA cleavage, cell viability, and antibiofilm activities of nanobioagents (1-4). The results were compared with those of unmodified rGO (nanobioagent 5), as well. Modification of reduced graphene oxide with the synthesized compounds improved its antioxidant activity. The antioxidant activities of all the tested nanobioagents also enhanced as the concentration increased. The antibacterial activities of all the nanobioagents improved by applying the photodynamic therapeutic (PDT) method. All the phthalonitrile/phthalocyanine-based nanobioagents (especially phthalocyanine-based nanocomposites) exhibited DNA cleavage activities, and complete DNA fragmentation was observed for nanobioagents (1-4) at 200 mg/L. They can be used as potent antimicrobial and antimicrobial photodynamic therapy agents as well as Escherichia coli microbial cell inhibitors. As a result, the prepared nanocomposites can be considered promising candidates for biomedicine.

Combination of phototherapy for treatment of labial necrotizing lesion

Lip necrotizing lesions are painful, complex to heal, and negatively impact the patient’s orofacial condition. The present study reports a clinical case of a necrotizing lesion on the lower lip in a 38-year-old male patient, previously healthy, f ive days after receiving the first dose of the SARS-COV-2 vaccine, with an initial diagnosis of labial herpes zoster, with secondary infection and unsatisfactory response to clinical treatment. After debridement of the necrotic tissue, followed by a combination of antimicrobial photodynamic therapy (aPDT), photobiomodulation therapy (PBMT) and hydrofiber dressing with silver, the patient evolved with complete healing of the lip lesion and satisfactory restoration of orofacial functions after 7 days. According to the present case report, this combination of phototherapy modalities suggests to be a promising tool for the treatment of necrotizing labial lesions.

Unveiling combat strategies against Candida spp. biofilm structures: Demonstration of photodynamic inactivation with innovative phthalocyanine derivatives

Antimicrobial resistance is an important problem for infection control and therapy. Microorganisms in biofilm structure are remarkably less susceptible to antimicrobials compared to planktonic cells. Increasing rates of resistance to antimicrobials have led to the development of new antimicrobial strategies. Antimicrobial photodynamic therapy (PDT) is an alternative treatment method that may contribute to the fields of infection control and treatment. This study aimed to investigate the antifungal activities of photosensitizers and the anti-biofilm activities of phthalocyanine derivatives on C. albicans and C. parapsilosis strains. The anti-biofilm effects of aPDT on the biofilm of Candida albicans were also visualized via SEM (Scanning Electron Microscopy). Our findings showed that aPDT with phthalocyanines inhibited biofilm production levels and reduced the mature biofilm levels of Candida strains. Additionally, SEM results supported that aPDT application successfully eradicated fungal cells and inhibited the biofilm produced by C. albicans. Although more detailed experiments are needed, we suggest that the use of Pcs in aPDT may be beneficial for the treatment of biofilm-related Candida infections.

Photodynamic and nitric oxide therapy-based synergistic antimicrobial nanoplatform: an advanced root canal irrigation system for endodontic bacterial infections

BackgroundThe main issues faced during the treatment of apical periodontitis are the management of bacterial infection and the facilitation of the repair of alveolar bone defects to shorten disease duration. Conventional root canal irrigants are limited in their efficacy and are associated with several side effects. This study introduces a synergistic therapy based on nitric oxide (NO) and antimicrobial photodynamic therapy (aPDT) for the treatment of apical periodontitis.ResultsThis research developed a multifunctional nanoparticle, CGP, utilizing guanidinylated poly (ethylene glycol)-poly (ε-Caprolactone) polymer as a carrier, internally loaded with the photosensitizer chlorin e6. During root canal irrigation, the guanidino groups on the surface of CGP enabled effective biofilm penetration. These groups undergo oxidation by hydrogen peroxide in the aPDT process, triggering the release of NO without hindering the production of singlet oxygen. The generated NO significantly enhanced the antimicrobial capability and biofilm eradication efficacy of aPDT. Furthermore, CGP not only outperforms conventional aPDT in eradicating biofilms but also effectively promotes the repair of alveolar bone defects post-eradication. Importantly, our findings reveal that CGP exhibits significantly higher biosafety compared to sodium hypochlorite, alongside superior therapeutic efficacy in a rat model of apical periodontitis.ConclusionsThis study demonstrates that CGP, an effective root irrigation system based on aPDT and NO, has a promising application in root canal therapy.

Nanomaterial-based drug-delivery system as an aid to antimicrobial photodynamic therapy in treating oral biofilm.

Diverse microorganisms live as biofilm in the mouth accounts for oral diseases and treatment failure. For decades, the prevention and treatment of oral biofilm is a global challenge. Antimicrobial photodynamic therapy (aPDT) holds promise for oral biofilm elimination due to its several traits, including broad-spectrum antimicrobial capacity, lower possibility of resistance and low cytotoxicity. However, the physicochemical properties of photosensitizers and the biological barrier of oral biofilm have limited the efficiency of aPDT. Nanomaterials has been used to fabricate nanocarriers to improve photosensitizer properties and thus enhance antimicrobial effect. In this review, we have discussed the challenges of aPDT used in dentistry, categorized the nanomaterial-delivery system and listed the possible mechanisms involved in nanomaterials when enhancing aPDT effect.

Reduction of microorganisms in carious dentin by photodynamic therapy mediated by potassium iodide added to methylene blue and red laser

ObjectiveTo evaluate the effect of the association of potassium iodide to antimicrobial photodynamic therapy on human carious dentin produced with a microcosm biofilm model. MethodsA microcosm biofilm model was used to generate a caries lesion on human dentin. Pooled human saliva diluted with glycerol was used as an inoculum on specimens immersed on McBain artificial saliva enriched with 1 % sucrose (24 h at 37 °C in 5 % CO2). After refreshing culture media for 7 days, the dentin specimens were divided in 5 groups (3 specimens per group, in triplicate; n = 9): C (NaCl 0.9 %), CX (2 % chlorhexidine), PKI (0.01 % methylene blue photosensitizer+50 mM KI), L (laser at 15 J, 180 s, 22.7 J/cm2), and PKIL (methylene blue + KI + Laser). After the treatments, dentin was collected, and a 10-fold serial dilution was performed. The number of total microorganisms, total lactobacilli, total streptococci, and Streptococcus mutans was analyzed by microbial counts (CFU/mL). After normality and homoscedasticity analysis, the Welch's ANOVA and Dunnett's tests were used for CFU. All tests used a 5 % significance level. ResultsCX and PKIL groups showed significant bacterial decontamination of dentin, compared to group C (p < 0.05) reaching reductions up to 3.8 log10 for CX for all microorganisms’ groups and PKIL showed 0.93, 1.30, 1.45, and 1.22 log10 for total microorganisms, total lactobacilli, total streptococci, and S. mutans, respectively. ConclusionaPDT mediated by the association of KI and methylene blue with red laser reduced the viability of microorganisms from carious dentin and could be a promising option for cavity decontamination.

Bacterial resistance to antimicrobial photodynamic therapy: A critical update

Bacterial antibiotic resistance is one of the most significant challenges for public health. The increase in bacterial resistance, mainly due to microorganisms harmful to health, and the need to search for alternative treatments to contain infections that cannot be treated by conventional antibiotic therapy has been aroused. An alternative widely studied in recent decades is antimicrobial photodynamic therapy (aPDT), a treatment that can eliminate microorganisms through oxidative stress. Although this therapy has shown satisfactory results in infection control, it is still controversial in the scientific community whether bacteria manage to develop resistance after successive applications of aPDT. Thus, this work provides an overview of the articles that performed successive aPDT applications in models using bacteria published since 2010, focusing on sublethal dose cycles, highlighting the main PSs tested, and addressing the possible mechanisms for developing tolerance or resistance to aPDT, such as efflux pumps, biofilm formation, OxyR and SoxRS systems, catalase and superoxide dismutase enzymes and quorum sensing.

Selective antibacterial and antibiofilm activity of chlorinated hemicyanine against gram-positive bacteria

Antibiotic-free therapies are highly needed due to the limited success of conventional approaches especially against biofilm related infections. In this direction, antimicrobial phototherapy, either in the form of antimicrobial photothermal therapy (aPTT) or antimicrobial photodynamic therapy (aPDT), have appeared to be highly promising candidates in recent years. These are local and promising approaches for antibiotic resistant bacterial infections and biofilms. Organic small photosensitizers (PSs) are extensively preferred in antimicrobial phototherapy applications as they offer a great opportunity to combine therapeutic action (aPTT, aPDT or both) with fluorescence imaging on a single molecule. In this study, the bactericidal effect of cationic chlorinated hemicyanine (Cl-Hem)-based type I PS, which can function as a dual aPDT/aPTT agent, was investigated on both planktonic cells and biofilms of different gram-positive (E. faecalis and S. epidermidis) and gram-negative bacteria (P. aeruginosa and K. pneumoniae) with and without 640 nm laser irradiation. Cl-Hem was shown to induce a selective phototheranostic activity against gram-positive bacteria (E. faecalis and S. epidermidis). Cl-Hem exhibited both dose and laser irradiation time dependent bactericidal effect on planktonic and biofilms of S. epidermidis. These results clearly showed that highly potent Cl-Hem can treat resistant microbial infections, while allowing fluorescence detection at the same time. High biofilm reduction observed with combined aPDT/aPTT action of Cl-Hem together with its non-cytotoxic nature points out that Cl-Hem is a promising PS for antibacterial and antibiofilm treatments.

Application of Mono and Trinuclear Cyclometalated Iridium (III) Complexes in Differential Bacterial Imaging and Antimicrobial Photodynamic therapy.

The application of transition metal complexes for antimicrobial photodynamic therapy (PDT) has emerged as an attractive alternative in mitigating a broad range of bacterial pathogens, including multidrug-resistant pathogens. In view of their photostability, long excited-state lifetimes, and tunable emission properties, transition metal complexes also contribute as bioimaging agents. In the present work, we designed mono and trinuclear cyclometalated iridium(III) complexes to explore their imaging application and antibacterial potential. For this, we used Methicillin-resistant S. aureus (MRSA), the most prevalent of community-associated (CA) multidrug-resistant (MDR) bacteria (CA MDR) and Lactococcus lactis (L. lactis) as Gram-positive while Campylobacter jejuni (C. jejuni) and E. coli as Gram-negative bacteria. In addition to differential bioimaging of these bacteria, we assessed the antibacterial effects of both mono and trinuclear Ir(III) complexes under exposure to 427 nm LED light. The data presented herein strongly suggest better efficacy of trinuclear Ir(III) complex over mononuclear complex in imparting photoinduced cell death of MRSA. Based on the safety profile of these complexes, we propose that trinuclear cyclometalated iridium(III) complex hold great promise for selective recognition and targeting MDR bacteria with minimal off-target effect.

Association of photobiomodulation and antimicrobial photodynamic therapy in healing after multiple extraction in head and neck post-radiotherapy- a case report and literature review

Association of photobiomodulation and antimicrobial photodynamic therapy in healing after multiple extraction in head and neck post-radiotherapy- a case report and literature review

Phthalocyanine‐Based Photosensitizers for Photodynamic Antibacterial Therapy

AbstractBacterial infection poses a grave peril to human existence and well‐being, particularly with the emergence of drug‐resistant bacteria, leading to an alarming rise in the incidence of severe illness and mortality. Antimicrobial photodynamic therapy (aPDT) has emerged as one of the most promising strategies for combating bacterial infections due to its potent bactericidal efficacy and non‐inducement of resistance. The development of novel photosensitizers represents a viable approach to further enhance the efficacy of aPDT. Hence, the structural design and application strategies of phthalocyanine‐based photosensitizers were summarized to provide guidance in the development of highly efficient aPDT agents.

SinoNasal Microbiota Transfer to treat recalcitrant chronic rhinosinusitis: A case series.

SinoNasal Microbiota Transfer (SNMT) was safe with immediate benefit in all recipients, with sustained improvement in two of three recipients for up to 180 days. The addition of antimicrobial photodynamic therapy worsened chronic rhinosinusitis. These promising SNMT results warrant further study of safety and efficacy.

In Vitro Antimicrobial Photodynamic Therapy for Pseudomonas aeruginosa (P. aeruginosa) and methicillin-resistant Staphylococcus aureus (MRSA) Inhibition Using a Green Light Source.

Photodynamic therapy (PDT) has been based on using photosensitizers (PS) and applying light of a specific wavelength. When this technique is used for treating infections, it is known as antimicrobial photodynamic therapy (aPDT). Currently, the use of lighting sources for in vitro studies using aPDT is generally applied in multiwell cell culture plates; however, depending on the lighting arrangement, there are usually errors in the application of the technique because the light from a well can affect the neighboring wells or it may be that not all the wells are used in the same experiment. In addition, one must be awarded high irradiance values, which can cause unwanted photothermal problems in the studies. Thus, this manuscript presents an in vitro antimicrobial photodynamic therapy for a Pseudomonas aeruginosa (P. aeruginosa) and methicillin-resistant Staphylococcus aureus (MRSA) inhibition study using an arrangement of thermally isolated and independently illuminated green light source systems for eight tubes in vitro aPDT, determining the effect of the following factors: (i) irradiance level, (ii) exposure time, and (iii) Rose Bengal (RB) concentration (used as a PS), registering the Pseudomonas aeruginosa (P. aeruginosa) and methicillin-resistant Staphylococcus aureus (MRSA) inhibition rates. The results show that in the dark, RB had a poor antimicrobial rate for P. aeruginosa, finding the maximum inhibition (2.7%) at 30 min with an RB concentration of 3 µg/mL. However, by applying light in a correct dosage (time × irradiance) and the adequate RB concentration, the inhibition rate increased by over 37%. In the case of MRSA, there was no significant inhibition with RB in complete darkness and, in contrast, the rate was 100% for those experiments that were irradiated.

Antimicrobial Photodynamic Therapy Using Encapsulated Protoporphyrin IX for the Treatment of Bacterial Pathogens.

Herein, we report on the antimicrobial photodynamic effect of polymeric nanoparticles containing the endogenous photosensitizer protoporphyrin IX. Compared to equivalent doses of the free photosensitizer, we demonstrated that the photodynamic antimicrobial efficacy of PLGA (polylactic-co-glycolic acid) nanoparticles containing protoporphyrin IX (PpIX) against pathogenic Staphylococcus aureus (S. aureus) is preserved after encapsulation, while photobleaching is reduced. In addition, compared to equivalent doses of the free porphyrin, we show that a reduction in the cytotoxicity in mammalian cell cultures is observed when encapsulated. Therefore, the encapsulation of protoporphyrin IX reduces its photodegradation, while the released photosensitizer maintains its ability to generate reactive oxygen species upon light irradiation. The polymeric nanoencapsulation promotes aqueous solubility for the hydrophobic PpIX, improves its photostability and reduces the cytotoxicity, while providing an extended release of this endogenous photosensitizer.

Multi-targets of antimicrobial photodynamic therapy mediated by erythrosine against Staphylococcus aureus identified by proteomic approach.

Staphylococcus aureus is a global challenge to the clinical field and food industry. Therefore, the development of antimicrobial photodynamic therapy (aPDT) has become one of the valuable methods to control this pathogen. The antibacterial activity of photoinactivation by erythrosine (Ery) against S. aureus has been reported, but its modes of action are unclear. This study aimed to employ a proteomic approach to analyze modes of action of Ery-aPDT against S. aureus. We determined the antibacterial effect by Ery-aPDT assays, quantified reactive oxygen species (ROS) and injury to the cell membrane, and determined protein expression using a proteomic approach combined with bioinformatic tools. Ery-aPDT was effective in reducing S. aureus to undetectable levels. In addition, the increment of ROS accompanied the increase in the reduction of cell viability, and damage to cellular membranes was shown by sublethal injury. In proteomic analysis, we found 17 differentially expressed proteins. These proteins revealed changes mainly associated with defense to oxidative stress, energy metabolism, translation, and protein biosynthesis. Thus, these results suggest that the effectiveness of Ery-aPDT is due to multi-targets in the bacterial cell that cause the death of S. aureus.

Antimicrobial photodynamic therapy for dermatological infections: current insights and future prospects

Introduction:Light-based antimicrobial photodynamic therapy (aPDT) shows promise against a wide range of microorganisms, including drug-resistant strains, with low resistance development likelihood. However, its limitations include the need for light exposure, suitability for local infections, and limited industry interest. Relevant studies on aPDT for various infections are discussed.Methods:We conducted an extensive literature review on aPDT encompassing articles published from the year 2000 to the current date. To compile comprehensive data, multiple databases (PubMed, Web of Science, Scopus, and Cochrane Library) were systematically searched for relevant studies in both English and Spanish languages. The search strategy involved a combination of Medical Subject Headings (MeSH) terms and free-text terms. The terms included variations and combinations of “Antimicrobial Photodynamic Therapy,” “aPDT,” “photodynamic inactivation,” “microbial photoinactivation,” among others. To ensure the reliability and quality of the information gathered, articles were screened based on relevance to aPDT in antimicrobial therapy, methodological rigor, and alignment with the objectives of this review.Results:aPDT shows promise in treating various cutaneous infections. It effectively targets fungal infections, including caused by dermatophytes and Malassezia spp., with notable results against dermatophytosis and tinea capitis. New photosensitizers, like nanoencapsulated hypericin, hold potential for treating these infections. In onychomycosis, aminolevulinic acid-aPDT or methylene blue-aPDT offers an alternative to conventional therapies, showing cure rates as high as 90%. For bacterial infections, it presents a solution against antibiotic-resistant strains and infected ulcers, with potential benefits for wound healing. Regarding viral infections, it indirectly targets viruses by impacting host cells’ metabolism, showing efficacy against human papillomavirus and herpes viruses. Lastly, aPDT demonstrates success in treating parasitic infections, particularly leishmaniasis, with cure rates of up to 100%.Discussion:aPDT is increasingly used in dermatological infections, showing efficacy against various microorganisms and stimulating wound healing. It can combat resistant strains and mixed infections, especially in chronic wounds. Combining photodynamic therapy with antimicrobials is a promising strategy to address antimicrobial resistance, but there are practical limitations. Further research is needed for home-based protocols, portable devices, and adapting photosensitizers, as aPDT holds potential as an alternative treatment for recalcitrant infections and immunosuppressed patients, though challenges remain in application.

Evaluation of antifungal activity of visible light-activated doped TiO2 nanoparticles.

Titanium dioxide (TiO2) is a well-known material for its biomedical applications, among which its implementation as a photosensitizer in photodynamic therapy has attracted considerable interest due to its photocatalytic properties, biocompatibility, high chemical stability, and low toxicity. However, the photoactivation of TiO2 requires ultraviolet light, which may lead to cell mutation and consequently cancer. To address these challenges, recent research has focused on the incorporation of metal dopants into the TiO2 lattice to shift the band gap to lower energies by introducing allowed energy states within the band gap, thus ensuring the harnessing of visible light. This study presents the synthesis, characterization, and application of TiO2 nanoparticles (NPs) in their undoped, doped, and co-doped forms for antimicrobial photodynamic therapy (APDT) against Candida albicans. Blue light with a wavelength of 450nm was used, with doses ranging from 20 to 60J/cm2 and an NP concentration of 500µg/ml. It was observed that doping TiO2 with Cu, Fe, Ag ions, and co-doping Cu:Fe into the TiO2 nanostructure enhanced the visible light photoactivity of TiO2 NPs. Experimental studies were done to investigate the effects of different ions doped into the TiO2 crystal lattice on their structural, optical, morphological, and chemical composition for APDT applications. In particular, Ag-doped TiO2 emerged as the best candidate, achieving 90-100% eradication of C. albicans.