A phthalocyanine-peptide conjugate for targeted photodynamic therapy of dental caries with concurrent tooth whitening effect.

Several resistance mechanisms are involved in dental caries, including oral biofilms. An accumulation of bacteria on the surface of teeth is called plaque. Periodontitis and gingivitis are caused by dental plaque. In this review article, we aimed to review the studies associated with the application of photodynamic therapy (PDT) to prevent and treat various microbial biofilm-caused oral diseases in recent decades. There are several studies published in PubMed that have described antimicrobial photodynamic therapy (APDT) effects on microorganisms. Several in vitro and in vivo studies have demonstrated the potential of APDT for treating endodontic, periodontal, and mucosal infections caused by bacteria as biofilms. Reactive oxygen species (ROS) are activated in the presence of oxygen by integrating a nontoxic photosensitizer (PS) with appropriate wavelength visible light. By causing irreversible damage to microorganisms, ROS induces some biological and photochemical events. Testing several wavelengths has been conducted to identify potential PS for APDT. A standard protocol is not yet available, and the current review summarizes findings from dental studies on APDT.

Background: Oral disorders, including tooth decay, periodontal disease, and endodontic infections, are prevalent worldwide. The escalating issue of antibiotic resistance exacerbates the need for alternative treatment modalities. Aim: This review aims to provide a comprehensive overview of advancements in photodynamic therapy (PDT) for dental applications, highlighting its potential as a non-invasive local and adjuvant therapy for various oral infectious disorders. PDT, which originated in the early 20th century, involves three primary components: A photosensitizer (PS), light, and oxygen. The PS selectively targets unwanted eukaryotic cells, such as tumors in the oral cavity, or pathogenic microorganisms, while sparing healthy cells. The efficacy of PDT is significantly influenced by the type of PS utilized. Method: An electronic search was conducted using the PubMed database focusing on peer-reviewed articles up to November 2023 using the keywords “photodynamic therapy,” “photochemotherapy,” “antimicrobial photodynamic therapy,” “antimicrobial photodynamic therapy oral,” resulting in 2341, 1034, 389, 221, and 96 items, respectively. After appropriate review, relevant data from other electronic sources are also included for additional information. Results: Historical and recent studies have demonstrated the effectiveness of porphyrin PSs and temoporfin in treating premalignant and malignant intraoral lesions, particularly as palliative treatments when conventional therapies have failed. In addition, phenothiazinium PSs, such as methylene blue and toluidine blue, have shown substantial antimicrobial activity against bacteria, viruses, and fungi. PDT has been applied successfully to treat specific oral conditions, including caries, endodontic and mucosal infections, periodontal disorders, and periimplantitis. Notably, its antibacterial properties suggest that PDT could reduce the dependency on systemic antibiotics. Conclusion: PDT emerges as a promising alternative to conventional treatments for oral infections, offering a potential solution to the global challenge of antibiotic resistance. Continued research and development are essential to enhance the effectiveness and broaden the application of PDT in dental care.

Objective To Study the effect of efflux pump-inhibitors(EPI)-Verapamil in photodynamic therapy (PDT) using hematoporphyrin monomethylether (HMME) as photosensitizer on the cariogenic bacteria in dental plaque biofilms.Methods According to the administrator order of the verapamil and photosensitizer in PDT,streptococcus mutans,streptococcus sanguis,eosinophilic lactobacillus and actinomyces viscosus were used to establish the dental plaque biofilm model.The experiment was divided into five groups,group A was incubated with the photosensitizer and verapamil group,group B using verapamil before incubated the photosensitize,group C suing photosensitizer before incubated verapamil,group D with PDT only,group E was control group.After laser treatment,the influence of the dental plaque biofilms was observed by confocal laser scanning microscope.Results As saline-treated group is a group of normal the dental plaque biofilms.In PDT only group,compared with the saline group,red fluorescence increased significantly,the bacteria lose accumulation capacity,and were isolated and scattered in dispersed state.In PDT plus verapamil group,compared with only PDT group,green staining increased,bacterial activity increased.In group B,cells were incubated with verapamil before incubated the photosensitizer group,green staining increased significantly,red fluorescence reduced,indicating live bacteria increased,and bacteria activity was significantly increased.Conclusion PDT is an effective method in eliminating cariogenic bacteria of dental plaque biofilms.Bacterial efflux pump inhibitors can lower HMME-PDT inhibition cariogenic bacteria in dental plaque biofilm,and pre-verapamil administration could significantly inhibit the effect of PDT treatment of dental caries. Key words: Photodynamic therapy; Dental caries; Plaque biofilm; Microbial efflux pump inhibitor; Confocal laser scanning microscopy

Objective To investigate the effects of photodynamic therapy(PDT) on the activity and structure of the dental plaque biofilm formed by the main cariogenic bacteria.Methods S.mutans,S.sangius,L.acidophilus and A.viscosus were chosen as the experimental bacteria to establish dental plaque biofilm model.They were separated into three groups:group of PDT、group of chlorhexidine and group of normal saline.The influence of the dental plaque biofilms was observed according to plate counting of bacteria method.The changes in the structure of biofilms after PDT were analyzed by means of confocal laser scanning microscopy.Results Compared to normal saline group,chlorhexidine cariogenic bacteria (CFU/ml) in plaque biofilms significantly reduced (P＜0.05),with the bactericidal rate 57.84％.After PDT treatment against artificial caries model,the number of cariogenic bacteria (CFU/ml) in plaque biofilms reduced more significantly (P＜0.05),the bactericidal rate up to 94.92％,and the structure of dental plaque biofilns changed evidently.Conclusion PDT is an effective method in eliminate cariogenic bacteria of dental plaque biofilms and to destroy the integrity of dental plaque biofilms,and it is a promising method for elimination of dental plaque and prevention of caries. Key words: Photodynamic therapy; Dental caries; Plaque biofilm; Confocal laser scanning microscopy

Scientific evidence in antimicrobial photodynamic therapy: An alternative approach for reducing cariogenic bacteria.

Dental caries, primarily caused by Streptococcus mutans (S. mutans) biofilms, remains a global health concern. Antimicrobial photodynamic therapy (aPDT) has shown promise in controlling cariogenic bacteria by generating reactive oxygen species (ROS), but the aggregation-caused quenching (ACQ) effect of traditional photosensitizers limits its efficacy. In this study, we developed a novel aggregation-induced emission (AIE) photosensitizer, CPTQ, with an enhanced photodynamic antibacterial efficacy and intrinsic antibacterial properties. CPTQ exhibited superior ROS generation, effective bacterial labeling, and strong membrane anchoring, leading to a significant disruption of bacterial membrane homeostasis and interference with bacterial metabolism. Moreover, CPTQ induced ferroptosis-like bacterial death by triggering lipid peroxidation and oxidative stress, providing a synergistic antibacterial strategy. In vitro results demonstrated that CPTQ effectively inhibited S. mutans growth, while in vivo studies in a rat dental caries model showed significant reductions in cariogenic bacterial load and caries progression. Given its excellent biocompatibility and dual antibacterial mechanisms, CPTQ offers a promising and innovative strategy for the prevention and treatment of dental caries.

Background: Oral biofilms are a major etiological factor in dental caries, periodontal disease, peri-implantitis, and endodontic infections. Increasing antimicrobial resistance and the limitations of conventional therapies have intensified interest in antimicrobial photodynamic therapy (aPDT). Hypericin, a natural photosensitizer derived from Hypericum perforatum, demonstrates potent reactive oxygen species generation and broad antimicrobial activity; however, its dental applications remain insufficiently synthesized. Objective: To systematically evaluate the antimicrobial efficacy, treatment parameters, safety, and clinical potential of hypericin-mediated aPDT against oral biofilms and infections in dentistry. Methods: This systematic review was conducted according to PRISMA 2020 and registered in PROSPERO CRD42024617727. Electronic searches of PubMed/MEDLINE, Embase, Scopus, and the Cochrane Library (January 2010 to December 2025) were performed. Studies assessing hypericin-mediated aPDT in oral or dental contexts were included. Methodological quality was evaluated using a predefined nine-domain risk-of-bias tool. Results: Eleven studies met the inclusion criteria. Hypericin-mediated aPDT demonstrated strong antimicrobial effects, achieving up to 99% planktonic inactivation and significant biofilm reduction across bacterial and fungal species. Activity was particularly pronounced against Gram-positive organisms, including Staphylococcus aureus and Enterococcus faecalis. However, efficacy against mature biofilms was variable and often dependent on formulation and irradiation parameters. Most studies showed moderate methodological quality, with frequent deficiencies in reporting light calibration and dosimetry. Advanced delivery systems, including liposomal and nanoparticle formulations, improved photodynamic performance. Conclusions: Hypericin-mediated aPDT shows promising antimicrobial activity against oral pathogens and biofilms, with favorable selectivity and safety profiles. Nevertheless, the evidence remains predominantly preclinical and heterogeneous. Standardized protocols and well-designed clinical trials are required before routine dental implementation can be recommended.

Dental caries is a multifactorial disease that affects a large proportion of the population with both genetic and environmental factors contributing to the disease. Even in healthy oral environmental conditions, some individuals are susceptible to dental caries due to potential genetic contribution. Antimicrobial peptides are expressed in oral cavity and play an important role against microbial colonization and form an important first line defense against cariogenic bacteria. In the present study, we attempt to identify genetic variants that would cause significant functional impact towards susceptibility to dental caries. We investigated single nucleotide polymorphisms (SNPs) of beta-defensin 1 (DEFB1) as predictors of dental caries in tamil ethnic population. A total of 120 subjects were recruited for this study, which included 60 dental caries patients (DMFT>5) and 60 healthy controls (DMFT=0). Three SNPs of 5’UTR regulatory elements of DEFB1 were genotyped by PCR followed by Sanger sequencing. The genotypes associated with susceptibility to caries were found to be significant between rs11362 (p=.025, odds ratio = 3.72, 95% confidence interval (CI) = 1.289-10.742), rs1799946 (p=.023, odds ratio=4.32, 95% CI = 1.33-14.028) gene polymorphisms and risk of dental caries (DMFT>5) in tamil ethnicity. The variant genotype GG of rs1800972 polymorphism was found to be high in cases than controls but was not significant (p=0.136). Our data suggested that β-defensin 1 polymorphisms play a role in the susceptibility to dental caries.

Objectives: The aim of the study was to design and synthesise novel lactotransferrin-derived antimicrobial peptides (AMPs) with enhanced antibacterial activity against cariogenic bacteria. Methods: We obtained the LF-1 (WKLLRKAWKLLRKA) and LF-2 (GKLIWKLLRKAWKLLRKA) AMPs, based on the N-terminal functional sequence of lactotransferrin, and characterised their physicochemical properties and secondary structure. Their antibacterial activity against caries-associated bacteria was evaluated using bacterial susceptibility and time-killing assays, as well as transmission electron microscopy (TEM). The antibiofilm activity against Streptococcus mutans biofilms was determined using biofilm susceptibility assays and confocal laser scanning microscopy (CLSM). A rodent model of dental caries was adopted to evaluate their anticaries effectiveness in vivo. Results: Both peptides possessed an α-helical structure with excellent amphipathicity. LF-1 was effective against S. mutans and Actinomyces species, whereas LF-2 showed more potent antibacterial activity than LF-1 against a broader spectrum of tested strains. Both peptides inhibited the formation of S. mutans biofilm starting at 8 μmol/L and exerted effective eradication of S. mutans in preformed biofilms. Both peptides exhibited satisfactory biocompatibility and exerted significant anticaries effects in a rodent model. Conclusion s: Both lactotransferrin-derived peptides displayed strong antimicrobial activity against cariogenic bacteria and S. mutans biofilm in vitro and effectively inhibited dental caries in vivo.

Oral microbial ecosystems are vital in maintaining the health of the oral cavity and the entire body. Oral microbiota is associated with the progression of oral diseases such as dental caries, periodontal diseases, head and neck cancer, and several systemic diseases such as cardiovascular disease, rheumatoid arthritis, adverse pregnancy outcomes, diabetes, lung infection, colorectal cancer, and pancreatic cancer. Buccal mucosa, tongue dorsum, hard palate, saliva, palatine tonsils, throat, keratinized gingiva, supra-gingival plaque, subgingival plaque, dentures, and lips are microbial habitats of the oral cavity. Porphyromonas gingivalis may have a role in the development of periodontal diseases, oral cancer, diabetes, and atherosclerotic disease. Fusobacterium nucleatum showed a higher abundance in periodontal diseases, oral and colon cancer, adverse pregnancy outcomes, diabetes, and rheumatoid arthritis. The higher abundance of Prevotella intermedia is typical in periodontal diseases, rheumatoid arthritis, and adverse pregnancy outcome. S. salivarius displayed higher abundance in both dental caries and OSCC. Oral bacteria may influence systemic diseases through inflammation by releasing pro inflammatory cytokines. Identification of oral bacteria using culture-dependent approaches and next-generation sequencing-based metagenomic approaches is believed to significantly identify the therapeutic targets and non-invasive diagnostic indicators in different human diseases. Oral bacteria in saliva could be exploited as a non-invasive diagnostic indicator for the early detection of oral and systemic disorders. Other therapeutic approaches such as the use of probiotics, green tea polyphenol, cold atmospheric plasma (CAP) therapy, antimicrobial photodynamic therapy, and antimicrobial peptides are used to inhibit the growth of biofilm formation by oral bacteria.

Current applications of drug delivery nanosystems associated with antimicrobial photodynamic therapy for oral infections

To evaluate the antibacterial efficacy of photodynamic therapy (PDT) and chitosan against Enterococcus faecalis and assess the possible enhancive effect of chitosan on the photosensitizer methylene blue in experimentally infected root canals of extracted human teeth in vitro. E. faecalis is frequently found in persistent endodontic infections. In this context, the antimicrobial PDT or newer antibacterial alternatives such as chitosan could become modern alternatives to existing antibacterial treatment approaches. One hundred two single-rooted extracted teeth were used. The teeth were contaminated with 0.1 mL E. faecalis (3 × 108 cell/mL). These were randomized into six treatment groups (n = 17 teeth): Group 1 (2.5% NaOCl); Group 2 (PDT); Group 3 (chitosan 3 mg/mL); Group 4 (PDT+chitosan 3 mg/mL); Group 5 (positive control, no treatment); and Group 6 (negative control, no inoculation, no treatment). The canal content was sampled with sterile paper points. The samples were cultured on blood agar plates to determine the number of colony-forming units (CFU)/mL. Five teeth in each group were analyzed by scanning electron microscope (SEM) to determine the percentage of area with contamination and debris. The positive control group showed the highest number of CFU/mL, with statistically significant differences in comparison with the other treatment groups (p ≤ 0.05). Group 4 (PDT+chitosan) showed the lowest CFU/mL count, followed by Group 2 (PDT alone), which obtained similar results to Group 1 (NaOCl), but there was no significance between the treated groups. SEM images showed that Group 4 (PDT+Chitosan) showed the lowest area of contamination. Combination of PDT and chitosan showed antibacterial potential against endodontic infection by E. faecalis.

Time-kill kinetic analysis of antimicrobial chemotherapy based on hydrogen peroxide photolysis against Streptococcus mutans biofilm

Adjunctive antimicrobial photodynamic therapy to conventional chemo-mechanical debridement of infected root canal systems: A systematic review and meta-analysis

Dental caries is a common and costly multifactorial biofilm disease caused by cariogenic bacteria that ferment carbohydrates to lactic acid, demineralizing the inorganic component of teeth. Therefore, low pH (pH 4.5) is a characteristic signal of the localised carious environment, compared to a healthy oral pH range (6.8 to 7.4). The development of pH-responsive delivery systems that release antibacterial agents in response to low pH has gained attention as a targeted therapy for dental caries. Release is triggered by high levels of acidogenic species and their reduction may select for the establishment of health-associated biofilm communities. Moreover, drug efficacy can be amplified by the modification of the delivery system to target adhesion to the plaque biofilm to extend the retention time of antimicrobial agents in the oral cavity. In this review, recent developments of different pH-responsive nanocarriers and their biofilm targeting mechanisms are discussed. This review critically discusses the current state of the art and innovations in the development and use of smart delivery materials for dental caries treatment. The authors’ views for the future of the field are also presented.