Search Results (215)

Infectious keratitis (IK), including bacterial, fungal, parasitic, and viral etiologies, continues to represent a significant cause of ocular morbidity in the United States and around the world. Corneal scraping for smears and cultures remains the gold standard in diagnosing IK; however, molecular diagnoses, including metagenomic deep sequencing (MDS), are promising emerging diagnostic tools. Despite recent interest in procedural treatment such as riboflavin photoactivated chromophore corneal collagen cross-linking (PACK-CXL) and Rose Bengal photodynamic antimicrobial therapy (RB-PDAT), medical treatment advances have remained stagnant. Methods: This review highlights IK pathogens obtained from corneal cultures at Bascom Palmer Eye Institute (BPEI) from 2011 to 2021 and provides the current BPEI algorithms for initial management of IK or as a referred clinically worsening patient. The roles of corticosteroid therapy, PACK-CXL, and RB-PDAT for IK are also summarized. Results: A total of 9326 corneal cultures were performed at BPEI between 2011 and 2021, and only 3609 (38.7%) had a positive organism identified, of which bacteria were the most common (83.4%). Fortified vancomycin and tobramycin are recommended as first-line medical therapy for IK patients based on culture sensitivity data for the top Gram-negative (Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) bacteria. PACK-CXL and RB-PDAT may benefit IK patients with corneal melting and fungal IK, respectively. Conclusions: Drug holidays, minimizing contamination, and optimizing sample order are crucial to maximizing corneal culture positivity. PACK-CXL and RB-PDAT are promising procedural advancements for IK therapy. Full article

Periodontitis is one of the most common inflammatory diseases and it is linked to the presence of a dysbiotic subgingival microbiome. The purpose of this review is to evaluate the impact of antimicrobial photodynamic therapy (aPDT) on the subgingival microbiome. Herein, based on an extensive evaluation of randomized controlled trials (RCTs), the effects of aPDT as a supplement to non-surgical periodontal therapy (NSPT) were found to be the main focus of these works. Studies that focused on analyzing microbiological results were selected, yielding contradictory results. The observed microbiological changes were variable, even though some studies showed notable improvements in clinical indicators such as bleeding on probing (BOP), clinical attachment level (CAL), and probing depth (PD). Several studies found that aPDT did not significantly reduce important periodontal pathogens such Tannerella forsythia, Porphyromonas gingivalis, and Aggregatibacter actinomycetemcomitans. Nevertheless, after multiple aPDT sessions, other studies reported positive changes in the subgingival microbiome, with a rise in beneficial bacteria and a decrease in periodontopathogens. While aPDT seems to be a safe and well-tolerated adjuvant to non-surgical periodontal therapy, there is still conflicting evidence regarding how well it modulates the subgingival microbiota. Additional long-term research with larger sample sizes is required to evaluate the microbiological and clinical advantages of aPDT. Full article

The alarming increase in infections caused by antimicrobial-resistant bacteria is increasingly posing a critical threat to public health. For this reason, the scientific community is focusing on alternative therapeutic strategies, such as antimicrobial photodynamic therapy (aPDT). This review examined the use of natural photosensitizers (PSs) in aPDT, emphasizing how they may produce high yields of reactive oxygen species when activated by light and consequently inactivate a wide range of pathogens, including bacteria embedded in biofilms, efficiently. The main methodologies and several strategies of incorporation into cutting-edge nanotechnological delivery systems of the most prevalent natural PSs (curcuminoids, perylenequinones, tetrapyrrolic macrocycles, and flavins) have been analyzed. Although natural PSs have benefits in terms of environmental sustainability and biocompatibility, their clinical use is frequently constrained by low bioavailability and solubility, issues that are being addressed more and more through novel formulations and dual-mode treatments. Studies conducted both in vitro and in vivo highlight these compounds’ strong antibacterial and wound-healing properties. In conclusion, natural molecule-based aPDT is a flexible and successful strategy for combating antimicrobial resistance, deserving of more translational study and clinical advancement. Full article

The growing threat of antimicrobial resistance has necessitated the development of alternative, non-antibiotic therapies for effective microbial control. Antimicrobial photodynamic therapy, which uses photosensitizers activated by light to generate reactive oxygen species, offers a promising solution. Among natural photosensitizers, curcumin, a polyphenolic compound from Curcuma longa, has demonstrated broad-spectrum antimicrobial activity through reactive oxygen species-mediated membrane disruption and intracellular damage. However, curcumin’s poor water solubility, low stability, and limited bioavailability hinder its clinical utility. Nanotechnology has emerged as a transformative strategy to overcome these limitations. This review comprehensively explores advances in nanocurcumin- and curcumin-loaded nanoparticles, highlighting their physicochemical enhancements, photodynamic mechanisms, and antimicrobial efficacy against multidrug-resistant and biofilm-associated pathogens. A range of nanocarriers, including chitosan, liposomes, nanobubbles, hybrid metal composites, metal–organic frameworks, and covalent organic frameworks, demonstrate improved microbial targeting, light activation efficiency, and therapeutic outcomes. Applications span wound healing, dental disinfection, food preservation, water treatment, and medical device sterilization. Conclusions and future directions are given, emphasizing the integration of smart nanocarriers and combinatorial therapies to enhance curcumin’s clinical translation. Full article

Background: This systematic review evaluated the efficacy of laser therapies and antimicrobial photodynamic therapy (aPDT) for the treatment of intraoral halitosis by synthesizing randomized controlled trials. Methods: A comprehensive search of the PubMed, Embase, Scopus, and Cochrane Library databases identified 14 eligible RCTs. Results: Laser-based interventions, including diode lasers and Er,Cr:YSGG lasers, and aPDT using photosensitizers such as methylene blue, toluidine blue, and Bixa orellana (annatto), effectively reduced volatile sulfur compound levels and associated bacterial populations compared to traditional methods like tongue scraping and antiseptic rinses. Combination treatments consistently demonstrated superior short-term efficacy, although treatment outcomes often declined after 7–14 days, indicating the necessity for repeated sessions or adjunctive oral hygiene measures. Conclusions: Methodological heterogeneity across studies regarding laser parameters, photosensitizer types, and outcome measurements highlighted the need for standardized protocols. Future research should focus on multicenter trials with extended follow-up and standardized microbiological evaluations to further validate these promising treatments and integrate them effectively into clinical practice. Full article

Municipal wastewaters pose a severe risk to the environment and human health when discharged untreated. This is due to their high content of pathogens, such as viruses and bacteria, which can cause diseases like cholera. Herein, the research and development of porphyrin-modified polyethersulfone (PES) ultrafiltration (UF) membranes was conducted to improve bacterial inactivation in complex municipal wastewater and enhance the fouling resistance and filtration performance. The synthesis and fabrication of porphyrin nanofillers and the resultant membrane characteristics were studied. The incorporation of porphyrin-based nanofillers improved the membrane’s hydrophilicity, morphology, and flux (247 Lm⁻² h⁻¹), with the membrane contact angle (CA) decreasing from 90° to ranging between 58° and 50°. The membrane performance was monitored for its flux, antifouling properties, reusability potential, municipal wastewater, and humic acid. The modified membranes demonstrated an effective application in wastewater treatment, achieving notable antibacterial activity, particularly under light exposure. The In-BP@SW/PES membrane demonstrated effective antimicrobial photodynamic effects against both Gram-positive S. aureus and Gram-negative E. coli. It achieved at least a 3-log reduction in bacterial viability, meeting Food and Drug Administration (FDA) standards for efficient antimicrobial materials. Among the variants tested, membranes modified with In-PB@SW nanofillers exhibited superior antifouling properties with flux recovery ratios (FRRs) of 78.9% for the humic acid (HA) solution and 85% for the municipal wastewater (MWW), suggesting a strong potential for long-term filtration use. These results highlight the promise of porphyrin-functionalized membranes as multifunctional tools in advanced water treatment technologies. Full article

Phthalocyanines (Pcs) are well-established photosensitizers in photodynamic therapy, valued for their strong light absorption, high singlet oxygen generation, and photostability. Recent advances have focused on covalently conjugating Pcs, particularly zinc phthalocyanines (ZnPcs), with a wide range of small bioactive molecules to improve selectivity, efficacy, and multifunctionality. These conjugates combine light-activated reactive oxygen species (ROS) production with targeted delivery and controlled release, offering enhanced treatment precision and reduced off-target toxicity. Chemotherapeutic agent conjugates, including those with erlotinib, doxorubicin, tamoxifen, and camptothecin, demonstrate receptor-mediated uptake, pH-responsive release, and synergistic anticancer effects, even overcoming multidrug resistance. Beyond oncology, ZnPc conjugates with antibiotics, anti-inflammatory drugs, antiparasitics, and antidepressants extend photodynamic therapy’s scope to antimicrobial and site-specific therapies. Targeting moieties such as folic acid, biotin, arginylglycylaspartic acid (RGD) and epidermal growth factor (EGF) peptides, carbohydrates, and amino acids have been employed to exploit overexpressed receptors in tumors, enhancing cellular uptake and tumor accumulation. Fluorescent dye and porphyrinoid conjugates further enrich these systems by enabling imaging-guided therapy, efficient energy transfer, and dual-mode activation through pH or enzyme-sensitive linkers. Despite these promising strategies, key challenges remain, including aggregation-induced quenching, poor aqueous solubility, synthetic complexity, and interference with ROS generation. In this review, the examples of Pc-based conjugates were described with particular interest on the synthetic procedures and optical properties of targeted compounds. Full article

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

The unique properties of phthalocyanines (Pcs), such as strong absorption, high photostability, effective singlet oxygen generation, low toxicity and biocompatibility, versatile chemical modifications, broad spectrum of antimicrobial activity, and synergistic effects with other treatment modalities, make them a preferred superior sensitizer in the field of antimicrobial photodynamic therapy. The photodynamic and sonodynamic activity of 3-(3-(diethylamino)phenoxy)propanoxy substituted silicon(IV) Pc were evaluated against bacteria and cancer cells. Stability and singlet oxygen generation upon light irradiation and ultrasound (1 MHz, 3 W) were assessed with 1,3-diphenylisobenzofuran. The phthalocyanine revealed high photostability in DMF and DMSO, although the singlet oxygen yields under light irradiation were low. On the other hand, the phthalocyanine revealed excellent sonostability and caused a high rate of DPBF degradation upon excitation by ultrasounds at 1 MHz. The silicon phthalocyanine presented significant bacterial reduction growth, up to 5 log against MRSA and S. epidermidis upon light excitation, whereas the sonodynamic effect was negligible. The phthalocyanine revealed high activity in both photodynamic and sonodynamic manner toward hypopharyngeal tumor (FaDu, 95% and 42% reduction, respectively) and squamous cell carcinoma (SCC-25, 96% and 62% reduction, respectively). The sensitizer showed ca. 30% aldehyde dehydrogenase inhibition in various concentrations and up to 85% platelet-activating factor acetylhydrolase for 0.25 μM, while protease-activated protein C was stimulated up to 66% for 0.75 μM. 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

The emergence of multidrug-resistant (MDR) bacteria and biofilm-associated infections has created a significant hurdle for conventional antibiotics, prompting the exploration of alternative strategies. Photodynamic therapy (PDT), a technique that utilizes photosensitizers activated by light to produce ROS, has emerged as a beacon of hope in the fight against MDR microorganisms. Among the natural photosensitizers, hypocrellins (A and B) have shown remarkable potential with their dual-mode photodynamic action, generating ROS via both Type I (electron transfer) and Type II (singlet oxygen) pathways. This unique action disrupts bacterial biofilms and inactivates MDR pathogens. The amphiphilic nature of hypocrellins further enhances their promise, enabling deep biofilm penetration and ensuring potent antibacterial effects even in hypoxic environments, surpassing the capabilities of synthetic photosensitizers. This study critically examines the antimicrobial properties of hypocrellin-based PDT, emphasizing its mechanisms, advantages over traditional antibiotics, and effectiveness against MDR pathogens. Comparative analysis with other photosensitizers, the role of nanotechnology-enhanced delivery systems, and future clinical applications are explored. Its combination with nanotechnology enhances therapeutic outcomes, providing a viable alternative to conventional antibiotics. Further clinical research is essential to optimize its application and integration into antimicrobial treatment protocols. 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

Photodynamic therapy (PDT) using indocyanine green (ICG) has gained attention as an adjunctive treatment for periodontitis due to its antimicrobial and anti-inflammatory properties and its ability to penetrate deep periodontal tissues via near-infrared light activation. We aimed to evaluate the clinical and microbiological efficacy of ICG-mediated PDT as an adjunct to conventional periodontal therapy in patients with periodontitis based on data from randomized controlled trials (RCTs). A systematic search of PubMed, Embase, Scopus, and the Cochrane Library was conducted to identify randomized controlled trials (RCTs) exclusively investigating ICG-PDT in periodontitis based on predefined eligibility criteria. Studies were selected based on predefined inclusion criteria, and methodological quality was assessed using a 14-point scoring system. Data were extracted on clinical outcomes (e.g., probing depth, clinical attachment level) and microbiological changes. Sixteen RCTs met the inclusion criteria. Most studies reported improvements in probing depth, clinical attachment level, and microbial reduction following ICG-aPDT; however, some trials found no significant differences compared to control groups. These discrepancies may be attributable to variations in laser settings, ICG concentration, treatment frequency, or initial disease severity. Microbiological benefits included significant reductions in key periodontal pathogens. The therapy was well tolerated, with no adverse effects reported. However, variability in treatment protocols and limited long-term follow-up restricted the ability to draw definitive conclusions. ICG-mediated PDT is a promising, safe, and effective adjunct in periodontal therapy. Future trials should aim for protocol standardization and long-term outcome assessment to strengthen clinical guidance. Full article