Targeting bacterial biofilm-related genes with nanoparticle-based strategies.

Persistent infection caused by biofilm is an urgent in medicine that should be tackled by new alternative strategies. Low efficiency of classical treatments and antibiotic resistance are the main concerns of the persistent infection due to biofilm formation which increases the risk of morbidity and mortality. The gene expression patterns in biofilm cells differed from those in planktonic cells. One of the promising approaches against biofilms is nanoparticle (NP)-based therapy in which NPs with multiple mechanisms hinder the resistance of bacterial cells in planktonic or biofilm forms. For instance, NPs such as silver (Ag), zinc oxide (ZnO), titanium dioxide (TiO2), copper oxide (Cu), and iron oxide (Fe3O4) through the different strategies interfere with gene expression of bacteria associated with biofilm. The NPs can penetrate into the biofilm structure and affect the expression of efflux pump, quorum-sensing, and adhesion-related genes, which lead to inhibit the biofilm formation or development. Therefore, understanding and targeting of the genes and molecular basis of bacterial biofilm by NPs point to therapeutic targets that make possible control of biofilm infections. In parallel, the possible impact of NPs on the environment and their cytotoxicity should be avoided through controlled exposure and safety assessments. This study focuses on the biofilm-related genes that are potential targets for the inhibition of bacterial biofilms with highly effective NPs, especially metal or metal oxide NPs.

In vitro antibiofilm effect of different irradiation doses in infected root canal model.

BACKGROUND: Eradication of endodontic biofilms from the infected root canal system is still the main concern in endodontics. In this study, the role of the power density parameter in the efficacy of antimicrobial photodynamic therapy (PDT) with toluidine blue O (TBO) and phycocyanin (PC) activated by a 635 nm diode laser (DL) against Enterococcus faecalis biofilm in the root canal model was investigated. MATERIALS AND METHODS: The E. faecalis biofilm in the root canal was treated with TBO and PC with different power densities (636, 954, 1273, and 1592 W/cm2). The untreated biofilm represented the control group. After the treatments, the biofilms were analyzed based on the number of colonies per milliliter. RESULTS: TBO and PC activated with 635 nm DL with a power density of 1592 W/cm2 were more efficient in removing E. faecalis biofilms within the root canals than those with a power density of 636 W/cm2 (p = 0.00). CONCLUSION: The light power density optimized the bacterial reduction of E. faecalis biofilms in the root canal spaces. These results provide information on the decisive parameters for performing PDT on intracanal biofilms.

Comparative study of the effect of different exposure parameters of 635nm diode laser and toluidine blue O in eliminating Aggregatibacter actinomycetemcomitans biofilm from titanium implant surfaces.

BACKGROUND: The aim of this study was to investigate the effects of antimicrobial photodynamic therapy (PDT) using 635 nm diode laser irradiation with an energy density of 6 to 30 J/cm2 and toluidine blue O (TBO) as a photosensitizer on the viability of Aggregatibacter actinomycetemcomitans attached to the surface of titanium implants. MATERIALS AND METHODS: Titanium implants contaminated with A. actinomycetemcomitans were treated with TBO alone or in combination with different exposure parameters (light doses of 6 - 30 J/cm2 at 635 nm) and 0.2 % chlorhexidine (CHX). After treatment, colony forming units (CFUs)/ml were determined to assess PDT efficacy. The structure of the biofilm of A. actinomycetemcomitans was analyzed by field emission scanning electron microscopy (FESEM). RESULTS: Under optimal conditions, the colony count was reduced by ∼90 %. Treatment with CHX was somewhat more effective (colony formation was reduced by ∼95 %), but this agent has adverse effects that can be avoided with PDT. CONCLUSION: This study confirms the efficacy of PDT against A. actinomycetemcomitans depending on the light dose. Treatment with TBO + 635 nm diode laser has an effect that may be equivalent to that of CHX, but perhaps with fewer adverse effects.

Simultaneous Dual-Wavelength Laser Irradiation against Implant-Adherent Biofilms of Staphylococcus aureus, Escherichia coli, and Candida albicans for Improved Antimicrobial Photodynamic Therapy.

The efficiency of antimicrobial photodynamic therapy (PDT) might be improved by using multiple wavelengths. This study investigates the sensitivity of implant-adherent biofilms of Staphylococcus aureus, Escherichia coli, and Candida albicans to indocyanine green (ICG)-808 nm diode laser, toluidine blue O (TBO)-635 nm diode laser, and hydrogen peroxide (HP)-980 nm diode laser and their combination when irradiated with dual-wavelength laser irradiation (simultaneously 980-635 nm or 980-808 nm). After an incubation period of 72 h, the infected implants were randomly divided into seven different treatment modalities: Control, HP, HP-PDT, TBO-PDT, HP-TBO-PDT, ICG-PDT, and HP-ICG-PDT. After the treatments, the colony-forming units (CFUs)/mL and reactive oxygen species (ROS) generation were determined. All evaluated disinfection methods were significantly effective against the three investigated bacteria compared to the control. The combined treatment of HP-ICG-PDT or HP-TBO-PDT had the greatest antibacterial effect compared to each treatment alone. There were statistical differences between HP-ICG-PDT and ICG-PDT or HP-TBO-PDT and TBO-PDT for all three bacteria studied. PDT with simultaneous dual-wavelength laser irradiation is an efficient strategy to improve the therapeutic effect of PDT.

In Vitro Assessment of SWEEPS and Antimicrobial Photodynamic Therapy Alone or in Combination for Eradicating Enterococcus faecalis Biofilm in Root Canals.

OBJECTIVES: This study investigates the efficacy of antimicrobial photodynamic therapy (aPDT) using riboflavin and a blue diode laser (BDL), combined with shock wave-enhanced emission photoacoustic streaming (SWEEPS), against Enterococcus faecalis. MATERIALS AND METHODS: A total of 48 extracted single-rooted human teeth were used. The root canals were instrumented, sealed at their apices, had the smear layer removed, and then underwent autoclave sterilization. Subsequently, each canal was inoculated with E. faecalis bacterial suspension and allowed to incubate for ten days. After confirming the presence of biofilms through scanning electron microscopy (SEM) in three teeth, the remaining teeth were randomly allocated into nine groups, each containing five teeth: control, 5.25% sodium hypochlorite (NaOCl), BDL, SWEEPS + normal saline, SWEEPS + NaOCl, riboflavin, riboflavin + SWEEPS, riboflavin + BDL, and riboflavin + BDL + SWEEPS. After the treatment, the numbers of colony-forming units (CFUs)/mL were calculated. The data were analysed using one-way ANOVA followed by Tukey's test for comparisons. RESULTS: All groups, with the exception of the BDL group, exhibited a significant reduction in E. faecalis CFU/mL when compared to the control group (p < 0.001). The difference in CFU/mL value between riboflavin + BDL + SWEEPS and riboflavin + SWEEPS was significant (p = 0.029), whereas there was no significant difference between riboflavin + BDL + SWEEPS and riboflavin + BDL (p = 0.397). Moreover, there was no statistically significant difference between the riboflavin + SWEEPS group and the riboflavin + BDL group (p = 0.893). CONCLUSIONS: The results demonstrated that combining the SWEEPS technique with riboflavin as a photosensitizer activated by BDL in aPDT effectively reduced the presence of E. faecalis in root canals.

Evaluating the effect of mechanical debridement with adjunctive antimicrobial photodynamic therapy in comparison with mechanical debridement alone on the peri-implant parameters in type 2 diabetic mellitus patients with peri-implantitis: a systematic review and meta-analysis.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a major risk factor for localized diseases such as peri-implantitis that may affect ideal implant treatment. This study was aimed to evaluate the effect of mechanical debridement (MD) + antimicrobial photodynamic therapy (a-PDT) in patients with peri-implantitis who have T2DM in terms of bleeding on probing (BOP) and probing depth (PD) as primary outcomes and plaque index (PI) and crestal bone loss (CBL) as secondary outcomes. METHODS: Publications compared outcomes between MD + aPDT and MD alone in T2DM patients with peri-implantitis, containing more than 3-month follow-up duration, were involved in the systematic review and meta-analysis. Literature until July 2023 using MEDLINE (through PubMed), Scopus, Cochrane Library, Embase, Web of Science, and Google Scholar were collected. RESULTS: Two randomized controlled trials (RCTs, 88 individuals) and one controlled clinical trial (CCT, 67 individuals) with follow-up periods ranged from 3 to 12 months were recruited. All studies used diode laser with wavelengths ranged from 660 to 810 nm. The results demonstrated that the MD + aPDT group showed significant benefits for BOP reduction after 6 months (SMD = -2.15, 95% CI: -3.78 to -0.51, p = 0.01). However, a great amount of heterogeneity was observed (I2 = 91.52%, p < 0.001). Moreover, there was a significant difference between MD + aPDT and MD alone groups in CBL (SMD = -0.69, 95% CI: -1.07 to -0.30, p < 0.001). In addition, homogeneity assumption was satisfied (I2 = 22.49%, p = 0.28). Significant differences in PD and PI reduction were not found except for PI reduction after 3 months (SMD = -0.79, 95% CI: -1.24 to -0.33, p < 0.001. Also, no heterogeneity was observed (I2 = 0.00%, p = 0.47). CONCLUSION: Given that high heterogeneity in BOP and PD outcome was found in this systematic review, future long-term CTs with MD + aPDT should be examined to arrive at a firm conclusion.

The Effect of Different Output Powers of Blue Diode Laser along with Curcumin and Riboflavin against Streptococcus mutans around Orthodontic Brackets: An In Vitro Study.

OBJECTIVES: The aim of the present study was to determine the effects of antimicrobial photodynamic therapy (aPDT) using the blue diode laser (BDL) with different output powers and the photosensitizers riboflavin and curcumin on reducing the number of Streptococcus mutans around orthodontic brackets. MATERIALS AND METHODS: A total of 36 orthodontic brackets were contaminated with S. mutans and randomly assigned to 12 groups as follows: control, riboflavin alone, riboflavin + BDL with an output power of 200, 300, 400, or 500 mW, and curcumin alone, curcumin + BDL with an output power of 200, 300, 400, or 500 mW, and 0.2% chlorhexidine (CHX-positive control). Orthodontic brackets were irradiated with a BDL (wavelength 445 nm) at a power density of 0.4-1.0 W/cm2 for 30 s. All orthodontic brackets were examined under a stereomicroscope at 10× magnification. Mean colony-forming units (CFUs)/mL were measured before and after treatment. A one-way analysis of variance with Tukey's post hoc test was performed to compare CFU/mL between groups. RESULTS: CHX and curcumin plus BDL with an output power of 500 mW had the highest reduction in S. mutans colony numbers (p < 0.001). The curcumin groups were more effective than the riboflavin groups. Riboflavin alone and riboflavin + BDL with an output power of 200 mW showed no significant difference from the control group (p = 0.99 and 0.74, respectively). CONCLUSION: Our results suggest that aPDT using curcumin as a photosensitizer plus BDL with an output power of 500 mW and a power density of 1.0 W/cm2 at a wavelength of 445 nm can effectively reduce colonies of S. mutans around stainless steel brackets.

The influence of different mode of power density during antimicrobial photodynamic therapy for photokilling of Streptococcus mutans.

BACKGROUND: The aim of this study was to evaluate the inactivation potency of riboflavin and curcumin plus blue diode laser against Streptococcus mutans with different power densities. MATERIALS AND METHODS: In this in vitro study, standard-strain S. mutans was exposed to curcumin and riboflavin plus blue diode laser with different power densities (0.4-1.0 W/cm2) as well as chlorhexidine (CHX). The colony forming units (CFUs)/mL was calculated. Data were analyzed by one-way ANOVA. RESULTS: Antibacterial analysis indicated that the blue diode laser irradiation with curcumin and riboflavin provided a satisfactory reduction of the S. mutans level. In addition, S. mutans was more affected by curcumin + blue diode laser when the power density was set to 1.0 W/cm2 (P < 0.0001). Meanwhile, bacterial suspensions treated with CHX showed maximum colony number reduction, compared with the control (P < 0.0001). CONCLUSION: This study showed the blue diode laser along with curcumin had strong bactericidal effect on S. mutans, and this effect improved by increasing the power density.

The Evaluation of SWEEPS Plus Antimicrobial Photodynamic Therapy with Indocyanine Green in Eliminating Enterococcus faecalis Biofilm from Infected Root Canals: An In Vitro Study.

OBJECTIVES: This study aimed to assess the efficacy of shockwave-enhanced emission photoacoustic streaming (SWEEPS) plus antimicrobial photodynamic therapy (aPDT) using indocyanine green (ICG) for the elimination of Enterococcus faecalis biofilm from infected root canals. MATERIALS AND METHODS: thirty sound human single-canal teeth were chosen and standardized to have 12 mm of root length. The root canals were shaped and prepared by means of ProTaper rotary files. After sterilization of the teeth, the canals were inoculated with E. faecalis for 2 weeks. The teeth were then randomly divided into six groups (n = five) of control, ICG, ICG + 808 nm diode laser, ICG + SWEEPS, ICG + 808 nm diode laser + SWEEPS, and 5.25% sodium hypochlorite (NaOCl). Following treatment, the number of colony-forming units (CFUs)/mL were calculated for each group. Statistical analysis was carried out using one-way ANOVA. For multiple comparisons, Tukey's test was used as the post hoc test. RESULTS: NaOCl alone showed the highest efficacy (p < 0.001). The ICG + 808 nm diode laser + SWEEPS group displayed significantly lower amounts of bacteria than either the ICG + 808 nm diode laser or SWEEPS (p < 0.001). There was a statistically significant difference detected between the ICG + 808 nm diode laser and ICG + SWEEPS (p = 0.035). CONCLUSIONS: SWEEPS can effectively increase the photosensitizer distribution in the root canal space, and its application along with irrigants can bring about promising results.

In vitro study of nanoliposomes containing curcumin and doxycycline for enhanced antimicrobial photodynamic therapy against Aggregatibacter actinomycetemcomitans.

The excessive inappropriate use of systemic antibiotics has contributed to the emergence of antibiotic-resistant pathogens, which pose a significant risk to the success of treatment. This study has approached this problem by developing doxycycline-loaded liposome doped with curcumin (NL-Cur+Dox) for combination antibacterial therapy against Aggregatibacter actinomycetemcomitans. The characterization of formulation revealed encapsulation of both drugs in NL-Cur+Dox with an average size of 239 nm and sustained release behavior. Transmission electron microscopy analysis confirmed the vesicular-shaped nanocarriers without any aggregation or crystallization. The cytotoxic and hemolytic activities of NL-Cur+Dox were evaluated. The anti-biofilm and anti-metabolic effects of NL-Cur+Dox -mediated antimicrobial photodynamic therapy (aPDT) were examined. The data indicated that NL-Cur+Dox -mediated aPDT led to a significant reduction of biofilm (82.7%, p = 0.003) and metabolic activity (75%, p < 0.001) of A. actinomycetemcomitans compared to the control. NL-Cur+Dox had no significant cytotoxicity to human gingival fibroblast cells under selected conditions (p = 0.074). In addition, the hemolytic activity of NL-Cur+Dox were negligible (< 5%). These findings demonstrate the potential application of such potent formulations in reducing one of the main bacteria causing periodontitis where the NL-Cur+Dox could be exploited to achieve an improved phototherapeutic efficiency.

The role of bacterial infections in rheumatoid arthritis development and novel therapeutic interventions: Focus on oral infections.

BACKGROUND: Rheumatoid arthritis (RA) represents a primary public health challenge, which is a major source of pain, disability, and socioeconomic effects worldwide. Several factors contribute to its pathogenesis. Infections are an important concern in RA patients, which play a key role in mortality risk. Despite major advances in the clinical treatment of RA, long-term use of disease-modifying anti-rheumatic drugs can cause serious adverse effects. Therefore, effective strategies for developing novel prevention and RA-modifying therapeutic interventions are sorely needed. OBJECTIVE: This review investigates the available evidence on the interplay between various bacterial infections, particularly oral infections and RA, and focuses on some potential interventions such as probiotics, photodynamic therapy, nanotechnology, and siRNA that can have therapeutic effects.

Antibacterial potential of riboflavin mediated blue diode laser photodynamic inactivation against Enterococcus faecalis: A laboratory investigation.

OBJECTIVES: This study aimed to evaluate the inactivation potency of riboflavin-mediated blue diode laser photodynamic inactivation (PDI) against Enterococcus faecalis at planktonic and biofilm stages and also investigated its effect on the tooth color change. MATERIALS AND METHODS: The antibacterial and antibiofilm activities of riboflavin mediated PDI against E. faecalis were investigated. The numbers of colony-forming units (CFUs)/mL were calculated. Teeth discoloration were evaluated using the CIE L*a*b* based color difference (ΔE). RESULTS: Antibacterial analysis indicated that the blue diode laser irradiation at 12, 18, 24, and 30 J/cm2 alone and different concentrations of riboflavin solution (6.25 to 100 µM) reduced the number of CFU/mL of E. faecalis, but the reduction was not statistically significant (P > 0.05). Depending on the riboflavin concentration and the light dose, there can be as much as a 1-log effect on CFU/mL. In addition, E. faecalis biofilm was more affected with 30 J/cm2 irradiation dosage and 100 µM riboflavin than other groups. Meanwhile, bacterial suspensions treated with 5.25% sodium hypochlorite (NaOCl) showed maximum biofilm inhibition and colony number reduction, compared with the control. The teeth exhibited clinically acceptable color change after riboflavin treatment at concentration ranging from 6.25 to 50 µM (ΔE < 3.7). CONCLUSIONS: The riboflavin mediated PDI process is somewhat less effective than NaOCl but perhaps less toxic to tissues. It might be feasible to repeat the riboflavin + light treatment to further promote efficacy.

An in vitro study on the efficacy of hydrogen peroxide mediated high-power photodynamic therapy affecting Enterococcus faecalis biofilm formation and dispersal.

OBJECTIVE: Biofilms are involved in failure of root canal treatment due to their high resistance to antimicrobial agents, which make their removal as a big challenge. The present study aims at utilizing hydrogen peroxide (HP) plus high frequency laser reinforced antimicrobial photodynamic therapy (a-PDT) as a complementary therapy against Enterococcus faecalis (E. faecalis) at planktonic and biofilm stages. MATERIALS AND METHODS: E. faecalis at planktonic and biofilm stages was treated with the photosensitizer HP, followed by no irradiation or irradiation with a power of 2.5 W (ʎ = 980 nm). The cell viability, anti-biofilm, anti-metabolic potential, and temperature changes were evaluated. RESULTS: The combination of HP and 980 nm diode laser intensely boosted antibacterial and anti-biofilm efficacy compared with either component alone, affirming HP reinforcement as a bacteriostatic agent. The maximum effect on biofilm occurs in 5.25% sodium hypochlorite (NaOCl) group. During laser irradiations, the mean of temperature changes remains below 5.6 °C. CONCLUSIONS: It could be concluded that the HP could improve anti-biofilm efficacy as a photosensitizer in a-PDT.

The Potential Application of Natural Photosensitizers Used in Antimicrobial Photodynamic Therapy against Oral Infections.

Oral health problems and the emergence of antimicrobial resistance among pathogenic bacterial strains have become major global challenges and are essential elements that negatively affect general well-being. Antimicrobial photodynamic therapy (APDT) is based on a light source and oxygen that activates a nontoxic photosensitizer, resulting in microbial destruction. Synthetic and natural products can be used to help the APDT against oral microorganisms. The undesirable consequences of conventional photosensitizers, including toxicity, and cost encourage researchers to explore new promising photosensitizers based on natural compounds such as curcumin, chlorella, chlorophyllin, phycocyanin, 5-aminolevulinic acid, and riboflavin. In this review, we summarize in vitro studies describing the potential use of APDT therapy conjugated with some natural products against selected microorganisms that are considered to be responsible for oral infections.

Comparison of bacterial disinfection efficacy using blue and red lights on dental implants contaminated with Aggregatibacter actinomycetemcomitans.

OBJECTIVES: The purpose of this study was to determine the bacterial disinfection efficacy of four photosensitizers (PSs; curcumin, riboflavin, toluidine blue O, and phycocyanin) with blue diode laser (Blue DL) and blue light-emitting diode (Blue LED) or Red DL and Red LED in dental implants contaminated with Aggregatibacter actinomycetemcomitans. MATERIALS AND METHODS: A total of 60 dental implants were contaminated with A. actinomycetemcomitans. All implants were then randomized into ten different disinfection modalities (n = 6 implants per group). The irradiation wavelength in Blue DL and Blue LED or Red DL and Red LED was 450, 430-460, 635, and 630 nm, respectively and its applied energy density was 60 J/cm2 in all groups. Group IX was served as the control group and in group X disinfection was performed with 0.2% chlorhexidine. After the treatments, the colony forming units (CFUs)/ml were calculated to determine antimicrobial effects of each treatment. RESULTS: All disinfection methods significantly reduced bacteria amounts of dental implants inoculated with A. actinomycetemcomitans compared to control group. The CFU/ml in LED group was significantly lower than the DL in all studied groups. CONCLUSION: aPDT could be an effective supplement in dental implants disinfection. The LED, proved to be better in reducing CFU/ml of A. actinomycetemcomitans on dental implants surface than DL.

Nanostructures as Targeted Therapeutics for Combating Oral Bacterial Diseases.

Pathogenic oral biofilms are now recognized as a key virulence factor in many microorganisms that cause the heavy burden of oral infectious diseases. Recently, new investigations in the nanotechnology field have propelled the development of novel biomaterials and approaches to control bacterial biofilms, either independently or in combination with other substances such as drugs, bioactive molecules, and photosensitizers used in antimicrobial photodynamic therapy (aPDT) to target different cells. Moreover, nanoparticles (NPs) showed some interesting capacity to reverse microbial dysbiosis, which is a major problem in oral biofilm formation. This review provides a perspective on oral bacterial biofilms targeted with NP-mediated treatment approaches. The first section aims to investigate the effect of NPs targeting oral bacterial biofilms. The second part of this review focuses on the application of NPs in aPDT and drug delivery systems.

Combinatorial therapy of chitosan hydrogel-based zinc oxide nanocomposite attenuates the virulence of Streptococcus mutans.

BACKGROUND: Biofilm formation is an important causative factor in the expansion of the carious lesions in the enamel. Hence, new approaches to efficient antibacterial agents are highly demanded. This study was conducted to evaluate the antimicrobial-biofilm activity of chitosan hydrogel (CS gel), zinc oxide/ zeolite nanocomposite (ZnONC) either separately or combined together [ZnONC / CS gel (ZnONC-CS)] against Streptococcus mutans biofilm. RESULTS: MTT assay demonstrated that the ZnONC-CS exhibits a non-cytotoxic effect (> 90% cell viability) toward human gingival fibroblast cells at different dosages (78.1-625 µg/mL) within 72 h. In comparison with CS gel and ZnONC, ZnONC-CS was superior at biofilm formation and metabolic activity reduction by 33 and 45%, respectively; (P < 0.05). The field emission scanning electron microscopy micrographs of the biofilms grown on the enamel slabs were largely in concordance with the quantitative biofilm assay results. Consistent with the reducing effect of ZnONC-CS on biofilm formation, the expression levels of gtfB, gtfC, and ftf significantly decreased. CONCLUSIONS: Taken together, excellent compatibility coupled with an enhanced antimicrobial effect against S. mutans biofilm has equipped ZnONC-CS as a promising candidate for dental biofilm control.

Effects of sub-lethal dose of antimicrobial photodynamic therapy on major virulence traits of Streptococcus mutans.

BACKGROUND: Antimicrobial photodynamic therapy (aPDT) as a complementary step of selective removal of dental caries appears as an ideal choice to help manage caries with minimal interventions. Sub-lethal dose of aPDT (sPDT) impressively effects microbial virulence, although it does not kill microorganisms. Therefore, the present study aimed to investigate the influence of sPDT using diode laser plus chlorophyllin-phycocyanin mixture (PhotoActive+) on changes in gtfB gene expression and the subsequent protein expression of GtfB. MATERIALS AND METHODS: sPDT using PhotoActive+ and 635 ± 10 nm diode laser was used to examine the expression of gtfB mRNA and GtfB protein expression of Streptococcus mutans by quantitative real time PCR (qRT-PCR) method and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), respectively. RESULTS: In this study, sPDT using 2.4 × 10-3 mol/L PhotoActive+ with 3 min irradiation time of diode laser with energy density of 104 J/cm2, significantly reduced the gtfB gene expression with rates of 3.5-fold (P < 0.05). Also, PhotoActive+ mediated sPDT demonstrated a significant reduction in GtfB protein expression of S. mutans up to 54 % (P < 0.05). CONCLUSIONS: This study demonstrated the potential effect of PhotoActive+ mediated sPDT on one of the most important virulence factors of S. mutans.

Propolis nanoparticle enhances the potency of antimicrobial photodynamic therapy against Streptococcus mutans in a synergistic manner.

Less invasive removal approaches have been recommended for deep caries lesions. Antimicrobial photodynamic therapy (aPDT) and propolis nanoparticle (PNP) are highlighted for the caries management plan. Evidence is lacking for an additive effect of combination PNP with photosensitizer (PS) in aPDT. This study aimed to investigate the individual and synergistic effects of chlorophyllin-phycocyanin mixture (PhotoActive+) and toluidine blue O (TBO) as PSs in combination with PNP in the aPDT process (aPDTplus) against major important virulence factors of Streptococcus mutans. Following characterization, biocompatibility of the PSs alone, or in combination with PNP were investigated on human gingival fibroblast cell. The in vitro synergy of PhotoActive+ or TBO and PNP was evaluated by the checkerboard method. The bacteria's virulence properties were surveyed in the presence of the PSs, individually as well as in combination. When the PSs were examined in combination (synergistic effect, FIC Index < 0.5), a stronger growth inhibitory activity was exhibited than the individual PSs. The biofilm formation, as well as genes involved in biofilm formation, showed greater suppression when the PSs were employed in combination. Overall, the results of this study suggest that the combination of PhotoActive+ or TBO with PNP with the least cytotoxicity effects and the highest antimicrobial activites would improve aPDT outcomes, leading to synergistic effects and impairing the virulence of S. mutans.

Therapeutic applications of nucleic acid aptamers in microbial infections.

Today, the treatment of bacterial infections is a major challenge, due to growing rate of multidrug-resistant bacteria, complication of treatment and increased healthcare costs. Moreover, new treatments for bacterial infections are limited. Oligonucleotide aptamers are single stranded DNAs or RNAs with target-selective high-affinity feature, which considered as nucleic acid-based affinity ligands, replacing monoclonal antibodies. The aptamer-based systems have been found to be talented tools in the treatment of microbial infections, regarding their promising anti-biofilm and antimicrobial activities; they can reduce or inhibit the effects of bacterial toxins, and inhibit pathogen invasion to immune cell, as well as they can be used in drug delivery systems. The focus of this review is on the therapeutic applications of aptamers in infections. In this regard, an introduction of infections and related challenges were presented, first. Then, aptamer definition and selection, with a brief history of aptamers development against various pathogens and toxins were reviewed. Diverse strategies of aptamer application in drug delivery, as well as, the effect of aptamers on the immune system, as the main natural agents of human defense against pathogens, were also discussed. Finally, the future trends in clinical applications of this technology were discussed.