Search Results (136)

The emergence and spread of antimicrobial resistance among pathogens are significantly reducing available therapeutic options, highlighting the urgent need for novel and complementary treatment strategies. Antimicrobial photodynamic therapy (aPDT) is a promising alternative approach that can overcome antimicrobial resistance through a multitarget mechanism of action, exerting direct bactericidal and fungicidal effects with minimal risk of resistance development. Although aPDT has shown efficacy against a variety of pathogens, data on its activity against large collections of clinical multidrug-resistant strains are still limited. In this study, we assessed the antimicrobial activity of the photosensitizer RLP068/Cl combined with a red light-emitting LED source at 630 nm (Molteni Farmaceutici, Italy) against a large panel of Gram-negative and Gram-positive bacterial strains harboring relevant resistance traits and Candida species. Our results demonstrated the significant microbicidal activity of RLP068/Cl against all of the tested strains regardless of their resistance phenotype, with particularly prominent activity against Gram-positive bacteria (range of bactericidal concentrations 0.05–0.1 µM), which required significantly lower exposure to photosensitizer compared to Candida and Gram-negative species (range 5–20 µM). Overall, these findings support the potential use of RLP068/Cl-mediated aPDT as an effective therapeutic strategy for the management of localized infections caused by MDR organisms, particularly when conventional therapeutic options are limited. Full article

The aim of this work is to evaluate the effectiveness of antimicrobial photodynamic therapy (aPDT) against oral MDR (multi-drug-resistant) Candida spp. infections related to orthodontic treatment with palatal expanders through in vitro study. Methods: PDT protocol: Curcumin + H₂O₂ was used as a photosensitizer activated by a 460 nm diode LED lamp, with an 8 mm blunt tip for 2 min in each spot of interest. In vitro simulation: A palatal expander sterile device was inserted into a custom-designed orthodontic bioreactor, realized with 10 mL of Sabouraud dextrose broth plus 10% human saliva and infected with an MDR C. albicans clinical isolate CA95 strain to reproduce an oral palatal expander infection. After 48 h of incubation at 37 °C, the device was treated with the PDT protocol. Two samples before and 5 min after the PDT process were taken and used to contaminate a Petri dish with a Sabouraud field to evaluate Candida spp. CFUs (colony-forming units). Results: A nearly 99% reduction in C. albicans colonies in the palatal expander biofilm was found after PDT. Conclusion: The data showed the effectiveness of using aPDT to treat palatal infection; however, specific patient oral micro-environment reproduction (Ph values, salivary flow, mucosal adhesion of photosensitizer) must be further analyzed. Full article

Objectives: We aimed to evaluate the efficacy of antimicrobial photodynamic therapy (aPDT) in promoting wound healing after the surgical removal of inferior third molars. Methods: Patients in need of unilateral mandibular third molar extraction were randomly assigned to either a test or control group before surgery. During the test, a photoactive substance activated with laser light (20 mW, 660 nm) was applied to the post-extraction site for 60 s before suturing to promote healing and disinfection. The control group did not receive any laser applications after tooth removal. The probing pocket depth (PPD), bleeding on probing (BOP), plaque index (PI), gingival recession (REC), and levels of clinical attachment loss (CAL) before surgery (T0), 14 days after surgery (T1), and after 3 months after surgery (T2) were evaluated for the adjacent second molar. Post-operative swelling, pain (VAS index), the number of painkillers taken, alveolar probing, and Landry’s healing index were recorded at T1. Results: Sixty-five patients, aged between 14 and 39 years, were assigned randomly to test (n = 32) or control (n = 33) groups. Five dropouts occurred. Post-operative swelling and the VAS index were significantly lower in the test group compared to the control (p = 0.002 and p = 0.04, respectively). All periodontal indexes except recession significantly worsened at T1 in both groups. After three months, a significant improvement for PPD, CAL, and PI was recorded in the test group compared to the control (p = 0.001). Conclusions: According to the results of this study, the use of aPDT seems to have a beneficial effect on post-operative swelling and pain, as well as the plaque index, in the short-term follow-up. Full article

Background: This systematic review aimed to assess the outcomes related to the use of antimicrobial photodynamic therapy (aPDT) as an adjunct to non-surgical periodontal treatment (NSPT) of patients affected by periodontitis and with type 2 diabetes mellitus (T2DM). Methods: PubMed, Cochrane Library, Scopus, and Web of Science (core collection) were queried up to January 2025. The PICO question investigated the comparison between T2DM patients undergoing NSPT with or without aPDT, in terms of improvement of clinical parameters. Two independent operators performed the study selection, data extraction, and risk of bias assessment (RoB-2 tool). The meta-analysis examined the reduction in bleeding on probing (BoP) and probing pocket depth (PPD) in sites > 4 mm, reporting mean difference (MD) and 95% confidence intervals (CIs). Results: Among 502 studies retrieved, 15 were finally included in the systematic review and meta-analysis. In T2DM individuals, the adjunct of aPDT to NSPT demonstrated a substantial reduction in BoP and PPD after 3 and 6 months compared to the use of NSPT alone. Conclusions: The outcomes of this systematic review suggest that adjunctive aPDT may provide additional benefit to NSPT in reducing inflammation in T2DM patients with periodontitis, indicating that this combined therapy could represent a potentially useful approach for individuals with T2DM. Review registration: registration in PROSPERO (International prospective register of systematic reviews) with ID CRD42024506295 on 6 February 2024. Full article

Photodynamic therapy (PDT) is a non-invasive therapeutic method with over a century of medical use, especially in dermatology, ophthalmology, dentistry, and, notably, cancer treatment. With an increasing number of clinical trials, there is growing demand for innovation in PDT. Despite being a promising treatment for cancer and bacterial infections, PDT faces limitations such as poor water solubility of many photosensitizers (PS), limited light penetration, off-target accumulation, and tumor hypoxia. This review focuses on chlorins—well-established macrocyclic PSs known for their strong activity and clinical relevance. We discuss how nanotechnology addresses PDT’s limitations and enhances therapeutic outcomes. Nanocarriers like lipid-based (liposomes, micelles), polymer-based (cellulose, chitosan, silk fibroin, polyethyleneimine, PLGA), and carbon-based ones (graphene oxide, quantum dots, MOFs), and nanospheres are promising platforms that improve chlorin performance and reduce side effects. This review also explores their use in Antimicrobial Photodynamic Therapy (aPDT) against multidrug-resistant bacteria and in oncology. Recent in vivo studies demonstrate encouraging results in preclinical models using nanocarrier-enhanced chlorins, though clinical application remains limited. Full article

The adjunctive use of antimicrobial photodynamic therapy (aPDT) has been investigated as a promising approach to enhance periodontal therapy. Methylene blue (MB) is the most commonly used photosensitizer due to its favorable characteristics, including a neutral pH and an absorption peak at 660 nm. Due to the considerable heterogeneity among studies and the lack of well-established clinical protocols, this study aims to conduct an integrative review to highlight the effects of MB-mediated aPDT as an adjunct to periodontal treatment. The inclusion criteria were randomized clinical trials that used MB as the PS, published between 2009 and 2024, with a minimum follow-up of three months. Studies included patients with periodontitis treated with SRP alone or in combination with aPDT. Of the 237 studies initially identified, 23 met the eligibility criteria and were included in this integrative review. The risk of bias was evaluated using the Cochrane criteria for randomized controlled trials. Although the included studies reported heterogeneous clinical outcomes, a general trend toward improvement in key periodontal parameters—probing depth, bleeding on probing, clinical attachment level, and plaque index—was observed when MB-mediated aPDT was used as an adjunct to conventional periodontal treatment. However, substantial variability in clinical protocols—including differences in photosensitizer concentration, type of light source, irradiation time, and frequency of application—limited the comparability of results across studies. Despite these methodological inconsistencies, current evidence suggests that MB-mediated aPDT holds promise as an adjunctive approach in periodontal therapy. Nevertheless, due to the clinical heterogeneity and the limited number of studies with long-term follow-up, its overall efficacy remains inconclusive. Further well-designed randomized controlled trials with standardized protocols and subgroup analyses are essential to validate its clinical relevance. Full article

Klebsiella pneumoniae is a Gram-negative, encapsulated bacterium recognized by the World Health Organization (WHO) as a critical priority for new therapeutic strategies due to its increasing multidrug resistance (MDR). Antimicrobial photodynamic therapy (aPDT) has emerged as a promising alternative to antibiotics, exhibiting a broad spectrum of action and multiple molecular targets, and has been proposed for the treatment of clinically relevant infections such as pneumonia. However, despite excellent in vitro photodynamic inactivation outcomes, the success of in vivo therapy still faces challenges, particularly due to the presence of lung surfactant (LS) in the alveoli. LS entraps photosensitizers, preventing these molecules from reaching microbial targets. This study investigated the potential of indocyanine green (ICG) in combination with the biocompatible polymer Gantrez™ AN-139 for the photoinactivation of K. pneumoniae. Initial in vitro experiments demonstrated that aPDT with ICG alone is effective against K. pneumoniae in a concentration- and light dose-dependent manner, achieving total eradication at 75 µg/mL of ICG and 150 J/cm² of 808 nm light. When aPDT was performed with similar parameters in the presence of LS, no bacterial killing was observed. However, a significant synergistic effect was observed when ICG (25 µg/mL) was combined with a low concentration of Gantrez™ AN-139 (0.5% m/v) in the presence of dipalmitoylphosphatidylcholine (DPPC), the main component of LS. This formulation resulted in a substantial reduction (3.6 log₁₀) in K. pneumoniae viability. These findings highlight the potential of Gantrez™ AN-139 as an efficient carrier to enhance the efficacy of ICG-mediated aPDT against K. pneumoniae, even in the presence of lung surfactant, a necessary step before the in vivo experiments. Full article

The global burden of fungal infections is rising at an alarming rate, with superficial, cutaneous, and mucosal mycoses among the most prevalent. Conventional treatments rely on oral and topical antifungal agents; however, these therapies are often limited by adverse effects, toxicity, frequent recurrence, and poor patient adherence due to prolonged treatment regimens. Moreover, the emergence of antifungal resistance and multidrug-resistant species such as Candidozyma auris and Trichophyton indotineae highlights the urgent need for alternative therapeutic strategies, such as antimicrobial photodynamic therapy (aPDT). aPDT is based on photophysical and photochemical processes involving a photosensitizer (PS), a light source, and molecular oxygen. When combined, these elements generate reactive oxygen species that selectively destroy microbial cells. In this review, we explore various PSs and their effectiveness in aPDT against infections caused by dermatophytes, Candida spp., and other pathogenic fungi. Promisingly, aPDT has demonstrated antifungal activity against both susceptible and resistant strains. In addition, aPDT has been successfully used in cases of mycoses unresponsive to conventional therapies, showing favorable clinical outcomes and overall safety. Current evidence supports aPDT as a valuable strategy for the management of cutaneous, mucosal, and superficial fungal infections and as a potential strategy to combat antifungal resistance. Full article

Oral candidiasis, commonly caused by Candida (C.) albicans and other non-albicans Candida species, increases resistance to conventional antifungal therapies. This study aimed to evaluate the in vitro efficacy of antimicrobial photodynamic therapy (aPDT) using a 450 nm diode laser in combination with curcumin and riboflavin against Candida spp. and Staphylococcus (S.) aureus. Reference strains of C. albicans, C. glabrata, C. krusei, and S. aureus were exposed to aPDT under varying incubation times and laser parameters, then viable microorganism cells (CFU) counts were assessed the microbial reduction, and statistical analyses were performed to evaluate significance. aPDT significantly reduced microbial viability in a time- and dose-dependent manner. Optimal incubation times were 20 min for Candida spp. and 10 min for S. aureus, with the highest efficacy observed at 400 mW and 120 s irradiation. The photosensitizer or laser alone had no significant antimicrobial effect. Curcumin/riboflavin-mediated aPDT is a promising alternative or adjunctive approach to conventional antimicrobial therapy, particularly for resistant oral infections. Full article

Candida albicans is a significant pathogen in various fungal infections, including oral candidiasis and denture stomatitis. As antifungal resistance rises globally, there is an urgent need for alternative treatment strategies. Antimicrobial photodynamic therapy (aPDT), utilizing a photosensitizer and light to produce reactive oxygen species (ROS), has emerged as a promising approach. Rose Bengal (RB), a xanthene dye, exhibits a high singlet oxygen quantum yield, making it a candidate for aPDT. However, its efficacy in C. albicans treatment has been inconsistent, particularly against biofilm-associated infections, which are more resistant to conventional therapies. This systematic review evaluates the efficacy of Rose Bengal-mediated aPDT in combating C. albicans infections by synthesizing data from studies conducted over the past decade. We focus on the effectiveness of RB across different experimental conditions, including planktonic and biofilm forms of C. albicans. The review also explores the synergy between RB and other agents, such as potassium iodide, and compares the outcomes of RB-mediated aPDT to other photosensitizers and conventional antifungal treatments. Despite its potential, RB-aPDT shows variable effectiveness due to differences in experimental protocols, such as the photosensitizer concentration, incubation times, and light parameters. The review identifies the key limitations, such as RB’s poor biofilm penetration and high dark toxicity at elevated concentrations, which hinder its clinical applicability. The combination of RB with potassium iodide enhances its antifungal efficacy, suggesting that further optimization could improve its clinical potential. Overall, while Rose Bengal-mediated aPDT holds promise as a novel antifungal treatment, further research is needed to standardize protocols, enhance delivery systems, and validate its efficacy in vivo and clinical settings. Full article

Photodynamic therapy (PDT) is a light-activated treatment that generates reactive oxygen species (ROS) to induce microbial cell death. As resistance to traditional antibiotics intensifies globally, PDT has emerged as a promising alternative or adjunctive antimicrobial strategy. Among various photosensitizers, Hypocrellin, a perylenequinone compound, has shown high ROS yield and broad-spectrum activity against bacteria and fungi. This systematic review evaluated the efficacy, safety, and therapeutic potential of Hypocrellin-mediated antimicrobial photodynamic therapy. Following PRISMA 2020 guidelines, a comprehensive literature search was conducted in PubMed, Embase, Scopus, and the Cochrane Library for studies published between 2015 and 2025. Eligible studies included in vitro and preclinical in vivo research using Hypocrellin as a photosensitizer. Quality and risk of bias were assessed using a structured nine-item checklist. Ten eligible studies, all conducted in China, were included. Hypocrellin-mediated aPDT significantly reduced microbial loads in both planktonic and biofilm states of resistant pathogens such as Candida albicans, Candida auris, Cutibacterium acnes, and Staphylococcus aureus. The treatment acted via ROS-mediated apoptosis, membrane disruption, and mitochondrial dysfunction, with minimal cytotoxicity to mammalian cells. Studies also reported enhanced efficacy when Hypocrellin was incorporated into nanocarriers, polymeric scaffolds, or combined with chemodynamic or photothermal therapies. However, substantial heterogeneity was observed in Hypocrellin concentrations, irradiation parameters, and outcome measures. Hypocrellin-based PDT exhibits potent antimicrobial activity and favorable safety in preclinical settings, supporting its potential as an alternative to conventional antibiotics. However, standardized treatment protocols and robust clinical trials are urgently needed to validate long-term safety and translational feasibility. These findings underscore the broader promise of PDT in addressing drug-resistant infections through a mechanism unlikely to induce resistance. Full article

Objectives: The synergistic effect of shock wave-enhanced emission photoacoustic streaming (SWEEPS) and antimicrobial photodynamic therapy (aPDT) in mandibular molar root canal disinfection remains underexplored, particularly against dual-species biofilms that better simulate clinical conditions. This study evaluates their combined antimicrobial efficacy against Enterococcus faecalis and Candida albicans biofilms and assesses potential tooth discoloration caused by riboflavin and nano-curcumin. Materials and Methods: The mesiobuccal canals of 57 extracted mandibular molars were inoculated with E. faecalis and C. albicans biofilms. The antimicrobial effects were assessed using riboflavin or nano-curcumin with a 450 nm diode laser (BDL), SWEEPS, or their combinations, compared to 5.25% NaOCl (positive control) and saline (negative control). Biofilm reduction was quantified by colony-forming units (CFUs/mL), and discoloration was evaluated using the ΔE metric in the CIE L*a*b* color space. Results: Both microorganisms showed a significant decrease in colony numbers in all experimental groups compared to the negative control (p < 0.001), except for E. faecalis, where no significant difference was observed between the riboflavin/nano-curcumin groups and the negative control. Combining riboflavin or nano-curcumin with SWEEPS or BDL significantly enhanced antimicrobial efficacy compared to individual treatments (p < 0.001). The combined photodynamic therapy and SWEEPS groups showed the lowest colony counts. The ΔE values were, on average, 1.81 for riboflavin and 1.09 for nano-curcumin. Conclusions: The combination of SWEEPS and aPDT effectively reduces E. faecalis and C. albicans biofilms in molars, supporting its potential as an adjunct in endodontic disinfection. Minimal discoloration further highlights its clinical applicability. Full article

The escalating global health crisis of antibiotic resistance, driven by the rapid emergence of multidrug-resistant (MDR) bacterial pathogens, necessitates urgent and innovative countermeasures. This review comprehensively examines the diverse mechanisms employed by bacteria to evade antibiotic action, including alterations in cell membrane permeability, efflux pump overexpression, biofilm formation, target site modifications, and the enzymatic degradation of antibiotics. Specific focus is given to membrane transport systems such as ATP-binding cassette (ABC) transporters, resistance–nodulation–division (RND) efflux pumps, major facilitator superfamily (MFS) transporters, multidrug and toxic compound extrusion (MATE) systems, small multidrug resistance (SMR) families, and proteobacterial antimicrobial compound efflux (PACE) families. Additionally, the review explores the global burden of MDR pathogens and evaluates emerging therapeutic strategies, including quorum quenching (QQ), probiotics, postbiotics, synbiotics, antimicrobial peptides (AMPs), stem cell applications, immunotherapy, antibacterial photodynamic therapy (aPDT), and bacteriophage. Furthermore, this review discusses novel antimicrobial agents, such as animal-venom-derived compounds and nanobiotics, as promising alternatives to conventional antibiotics. The interplay between clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas) in bacterial adaptive immunity is analyzed, revealing opportunities for targeted genetic interventions. By synthesizing current advancements and emerging strategies, this review underscores the necessity of interdisciplinary collaboration among biomedical scientists, researchers, and the pharmaceutical industry to drive the development of novel antibacterial agents. Ultimately, this comprehensive analysis provides a roadmap for future research, emphasizing the urgent need for sustainable and cooperative approaches to combat antibiotic resistance and safeguard global health. Full article

Background/Objectives: Individuals with Down syndrome (DS) often present with severe periodontal disease at a young age. Adjuvant treatments to scaling and root planing (SRP), such as antimicrobial photodynamic therapy (aPDT), may benefit this population. This study evaluated the effectiveness of aPDT as an adjunct to SRP in individuals with DS. A randomized, double-blind, parallel trial was conducted with 37 individuals with DS. Methods: The test group (aPDT; n = 18) received SRP + aPDT, while the control group (C group; n = 19) received SRP only. For aPDT, a red laser (658 nm; 0.1 W; 2229 J/cm²; 40 s sweeping with optical fiber) combined with methylene blue (MB) (100 µg/mL) was applied across repeated sessions (on days 3, 7, and 14). Clinical parameters, such as plaque index (PI), clinical attachment level (CAL), probing depth (PD), and bleeding on probing (BOP), were recorded at baseline and after 3, 6, and 12 months of treatment. Statistical analyses were performed using parametric and non-parametric tests (p < 0.05). Results: Both treatments promoted improvements in all clinical periodontal parameters (p < 0.05). The aPDT group showed a statistically significant reduction in CAL at 3 months (aPDT = 4.58 mm vs. C = 4.72 mm; p < 0.05) and 12 months (aPDT = 4.59 mm vs. C = 4.84 mm; p < 0.05). Conclusions: aPDT improved periodontal health in the long term through a stable gain in attachment. Full article

Background/Objectives: Diabetes mellitus and periodontitis share a significant, bidirectional relationship. Diabetes raises the risk of periodontitis and influences its severity, impacting tissue repair and bone metabolism. Conversely, periodontal inflammation can disrupt glycemic control, further complicating this interlinked relationship. This systematic review aimed to evaluate the efficacy of antimicrobial photodynamic therapy (aPDT) as an adjunct to subgingival instrumentation (SI) in the treatment of periodontal pockets with a probing pocket depth (PPD) ≥ 5 mm in individuals with type 2 diabetes mellitus (DM2) and periodontitis. Methods: Using the PICOS framework, this review addressed the following question: “How does aPDT as an adjunct to SI compare to SI alone in treating periodontal pockets with PPD ≥ 5 mm in individuals with DM2 and periodontitis?” Databases searched included PubMed, Scopus, and Web of Science up to December 2024. Randomized clinical trials evaluating periodontal status and HbA1c levels in patients with DM2 undergoing periodontal therapy and experiencing SI were included. Patients who received adjunctive aPDT were compared to a control group that received SI alone. A meta-analysis was conducted illustrating treatment effects across groups. Results: After screening 117 studies based on titles and abstracts, three and four studies met the eligibility criteria for quantitative and qualitative analyses, respectively. The principal periodontal parameters assessed included PPD, clinical attachment level (CAL), plaque index (PI), and bleeding on probing (BOP). Forest plots for PD, BOP, PI, and CAL at baseline, three months, and six months revealed no statistically significant differences between the SI+aPDT group and the SI-only group. Glycated hemoglobin across treatment groups was not different. Conclusions: The combination of aPDT with SI provides limited clinical benefits in treating periodontal pockets with a PPD ≥ 5 mm in diabetic patients with periodontitis. Full article