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Bacterial antibiotic resistance is one of the most significant challenges for public health. The increase in bacterial resistance, mainly due to microorganisms harmful to health, and the need to search for alternative treatments to contain infections that cannot be treated by conventional antibiotic therapy has been aroused. An alternative widely studied in recent decades is antimicrobial photodynamic therapy (aPDT), a treatment that can eliminate microorganisms through oxidative stress. Although this therapy has shown satisfactory results in infection control, it is still controversial in the scientific community whether bacteria manage to develop resistance after successive applications of aPDT. Thus, this work provides an overview of the articles that performed successive aPDT applications in models using bacteria published since 2010, focusing on sublethal dose cycles, highlighting the main PSs tested, and addressing the possible mechanisms for developing tolerance or resistance to aPDT, such as efflux pumps, biofilm formation, OxyR and SoxRS systems, catalase and superoxide dismutase enzymes and quorum sensing., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest. The funders had no role in the design of the study; in the collection, analysis, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In our previous studies, Chlorin-e6 (Ce6) demonstrated a significant reduction of microorganisms' viability against multi-species biofilm related to periodontitis while irradiated with blue light. However, the conjugation of Ce6 and antimicrobial peptides, and the incorporation of this photosensitizer in a nanocarrier, is still poorly explored. We hypothesized that chlorin-e6 conjugated to the antimicrobial peptide LL-37 loaded nanoemulsion could inhibit a multi-species biofilm related to periodontitis during photodynamic therapy (PDT), the pre-treatment with hydrogen peroxide was also tested. The nanoemulsion (NE) incorporated with Ce6 was characterized regarding the physiochemical parameters. Images were obtained by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Later, the Ce6 and LL-37 incorporated in NE was submitted to UV-Vis analysis and Reactive Oxygen Species (ROS) assay. Finally, the combined formulation (Ce6+LL-37 in nanoemulsion) was tested against multi-species biofilm related to periodontitis. The formed nanoformulation was kinetically stable, optically transparent with a relatively small droplet diameter (134.2 unloaded and 146.9 loaded), and weak light scattering. The NE system did not impact the standard UV-VIS spectra of Ce6, and the ROS production was improved while Ce6 was incorporated in the NE. The combination of Ce6 and LL-37 in NE was effective to reduce the viability of all bacteria tested. The treatment with hydrogen peroxide previous to PDT significantly impacted bacterial viability. The current aPDT regimen was the best already tested against periodontal biofilm by our research team. Our results suggest that this combined protocol must be exploited for clinical applications in localized infections such as periodontal disease. - Nanoemulsion demonstrated to be an excellent nanocarrier for photodynamic application. - Chlorin-e6 incorporated in nanoemulsion showed great physicochemical and biophotonic parameters. - The combination of chlorin-e6 and LL-37 peptide in nanoemulsion is effective to eliminate periodontal pathogenic bacteria. - The treatment with hydrogen peroxide previous to PDT significantly impacted bacterial viability., Competing Interests: Declaration of Competing Interest This manuscript has been read and approved in final form by all authors and the authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

In this study, the action of antimicrobial peptide (AMP) P5 and antimicrobial photodynamic therapy (aPDT) mediated by bixin and chlorin-e6 (Ce6) on Cutibacterium acnes (C. acnes) in planktonic phase and biofilm were evaluated both as monotherapies and combined therapies. Microbial viability after treatments were quantified by colony-forming units per milliliter of the sample (CFU/mL) and have demonstrated that all treatments employed exerted bactericidal activity, reducing the microbial load by more than 3 log 10 CFU/mL, also demonstrating for the first time in the literature the antimicrobial photodynamic effect of bixin that occurs mostly through type I mechanism which was proved by the quantification of superoxide anion production. Bacterial biofilm was completely eliminated only after its exposure to aPDT mediated by this PS, however, Ce6 proved to be a more efficient PS, considering that most of the photodynamic effect of bixin- aPDT was exerted by excitation of the endogenous C porphyrins of C. acnes with blue light. The combination of P5 with Ce6-aPDT showed a synergistic effect on the bacterial biofilm with a reduction in microbial load by more than 10 log 10 CFU/mL, in which the ability of P5 to permeabilize the polymeric extracellular matrix of the biofilm explains the obtained results, with greater internalization of the PS as shown by the Confocal Laser Scanning Microscopy. One-way ANOVA (Analysis of Variance) with Tukey's post-test and two-way ANOVA with Bonferroni's post-test were used to compare the values of continuous variables between the control group and the treatment groups., Competing Interests: Disclosure of author of conflicts of interest The authors declare that there are no conflicts of interest., (Copyright © 2022. Published by Elsevier B.V.)

Photodynamic therapy (PDT) is a therapeutic modality with high contributions in the treatment of cancer. This approach is based on photophysical principles, which presents as a less invasive strategy than conventional therapies. Combined with nanotechnology, the therapy becomes more efficient because nanoparticles (NPs) have advantageous characteristics such as biocompatibility, controlled, and targeted release, promoting solubility and decreasing the toxicity and side effects involved. In this work were developed nanoemulsions containing the methylene blue photosensitizer (MB) (MB/NE) and in the empty form (unloaded/NE). Subsequently, the mentioned nanomaterials were characterized by the measurement of dynamic light scattering (DLS). The MB/NE and unloaded/NE showed appropriate physical and chemical characteristics, with particle size ≤ 200 nm, polydispersity index close to 0.3, and zeta potential exhibiting negative charge, showing stable values during the analysis. The incorporation of the MB did not cause changes in the photophysical profile of the photosensitizer. The quantification performed showed an incorporation rate of 81.9%. Viability studies showed an absence of cytotoxicity for MB/NE in the concentrations of 10-75 µmol·L -1 , free MB at the concentration of 75 µmol·L -1 , and unloaded NE 47.5% (v/v), presenting viability close to 90%, respectively. PDT in vitro protocols applied to OSCC and HeLa cells showed a decrease in cell viability through only one irradiation, evidencing the photodynamic activity of the formulation when applied to cancer cells. The results obtained were superior to those found in the literature where they use free MB, showing that the association between nanotechnology and PDT optimizes the proposed protocol. From the results obtained, it is possible to indicate that the NE have high stability, with satisfactory physical-chemical parameters, in addition to not presenting cytotoxicity in the tested concentrations, showing their in vitro biocompatibility, in addition to presenting satisfactory effects when combined MB/NE with PDT, showing the potential of MB/NE as a very promising nanostructured photosensitizer for the treatment of some types of cancer., (© 2022. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Background: Although Curcumin (CUR) has great potential as a photosensitizer, the low solubility in water impairs its clinical performance in photodynamic inactivation (PDI). This study sought to establish an effective antimicrobial protocol for PDI using CUR in three different bioadhesive formulations., Methods: A CUR-loaded chitosan hydrogel with a poloxamer (CUR-CHIH), a CUR-loaded liquid crystal precursor system (CUR-LCP), a CUR-loaded microemulsion (CUR-ME), and CUR in dimethylsulfoxide (DMSO) solution (CUR-S; control formulation) were tested against in vitro and in situ oral biofilms. The optical properties of each formulation were evaluated., Results: All of the formulations exhibited lower absorbance than CUR-S; however, the CUR-LCP curve bore the highest resemblance. The CUR present in all formulations was completely degraded after 15 min of illumination. In vitro experiments showed that CUR-S was the only formulation able to significantly reduce biofilm viability of Candida albicans and Lactobacillus casei when compared to the negative control (no PDI); the amount of reduction obtained was 1.8 and 3.7 log (CFU/mL) for C. albicans and L. casei, respectively. There was a significant reduction on the viability of Streptococcus mutans biofilms when CUR-S and CUR-LCP were applied (approximately 3.5 and 1.6 log [CFU/mL], respectively). In situ testing showed antimicrobial efficacy against S. mutans and general microorganisms., Conclusions: Although the evaluated protocols has not been effective to all of the evaluated microorganisms, PDI showed potential against dental biofilms and evidence that the phototoxic effects of CUR have a high relation with the type of formulation in which it is loaded., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The oral cavity is colonized by several species of microorganisms that can cause dental caries, periodontal diseases, candidiasis, endodontic infections, and, among other diseases related to the dental field. Conventional treatment consists of mechanical removal associated with systemic administration of antimicrobials, which can cause various side effects and microbial resistance. In this context, alternative therapies have been developed, including Antimicrobial Photodynamic Therapy (aPDT). For the improvement of therapy, the implementation of nanotechnology is very important to optimize the delivery system of the dyes or photosensitizers on biological targets. Besides, this combination provides a non-invasive treatment, better solubility and bioavailability, delivery to the target site, controlled release and protection against external and physical-chemical factors, low side effects, and, unlikely resistant species. Although, there are numerous researches on aPDT and nanotechnology, few review articles based on the combination of these three aspects: nanosystems, aPDT and oral infections are available. For this reason, this article aims to discuss the advances and advantages of this combination. Therefore, this article was divided into different types of nanosystems (organic and inorganic nanoparticles) associated with aPDT bringing a description of it is definitions, properties, and, applications in oral infections., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In this work, we describe the synthesis and characterization of the SPIONP-CUR conjugate between curcumin (CUR) and superparamagnetic iron oxide nanoparticles (SPIONPs), in addition to its application in photodynamic therapy (PDT) using a protocol free of organic solvents as a dispersant. The SPIONP-CUR conjugate was characterized by X-ray diffraction, transmission electron microscopy, zeta potential measurements, Fourier transform infrared spectroscopy, thermogravimetry, magnetometry and magnetic hyperthermia assays. The SPIONP-CUR conjugation occurred by bonding between the keto-enol moiety of CUR and the iron atoms present on the surfaces of the SPIONPs. The conjugate showed heating power under an alternating magnetic field (AMF) and photodynamic action when irradiated with blue LED light. In experiments using PDT against Staphylococcus aureus in the planktonic phase, it was demonstrated that with application of blue light at 3.12 J cm -2 , the conjugate (dispersed in water) caused a total reduction of the bacterial load. In the absence of light, the reduction was insignificant, even after 24 h of contact with the bacteria., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This study aimed to evaluate the effect of the continuous irradiation with low intensity (continuous mode) and fractioned irradiation with high intensity (fractionated mode), keeping the same dose of light by using Light Emitting Diode (LEDs) with wavelength emission centered at 450 and at 660 nm, using methylene blue (MB), chlorin-e6 (Ce 6 ) and curcumin (CUR) as photosensitizers (PSs) against planktonic phase of E. faecalis. Cell viability was assessed by counting colonies forming per mL (CFU/mL), and the quantification of reactive species was performed by fluorescence with the photodegradation rate evaluated by measurements of absorbance of PSs at different times. The results revealed that MB-mediated PDT was efficient to achieve total microbial load reduction in both irradiation modes, but in fractional mode it was possible to use a lower light dose. Using Ce 6 , a total bacterial reduction was observed when fractional light was used, but at the same light dose, there was no reduction in the continuous irradiation mode. CUR-mediated PDT under continuous irradiation mode promoted the total microbial load reduction. However, for fractional mode, a higher concentration of CUR was required to completely reduce E. faecalis cell viability. Our results suggest that the biological response to PDT is variable depending on the irradiation mode and on the photosensitizer. Therefore, these studies indicate that the irradiation mode, intensity and the specific PSs should be taken into account for the development of clinical protocols for PDT., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The antimicrobial photodynamic therapy (aPDT) has stood out as an alternative and promising method of disinfection and has been exploited for the treatment of oral bacteria. In this study, we evaluate in vitro the action of aPDT, mediated by methylene blue, chlorin-e6, and curcumin against clinical subgingival plaques that were resistant to metronidazole. The sensitivity profile of the samples to metronidazole was analyzed by the agar dilution method. Cell viability in the planktonic and biofilm phase was assessed by CFU / mL. The composition of the biofilm was evaluated by the checkboard DNA-DNA Hibrydization technique. Photosensitizers internalization was qualitatively assessed by confocal fluorescence microscopy (CLSM). The aPDT mediated by the three photosensitizers tested was able to reduce the totality of the planktonic microbial load and partially reduce the biofilm samples. The analysis performed by CLSM showed that the photosensitizers used in the application of aPDT were able to permeate the interior of the biofilm. The aPDT has been shown to be useful in a supportive and effective approach to the treatment of periodontal disease., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Recent scientific research has shown the use of chlorin, phthalocyanines, and porphyrins derivatives as photosensitizers in photodynamic therapy in the treatment of various pathologies, including some of the major skin diseases. Thus, the main goal of this critical review is to catalog the papers that used these photosensitizers in the treatment of acne vulgaris, psoriasis, papillomavirus infections, cutaneous leishmaniasis, and skin rejuvenation, and to explore the photodynamic therapy mechanisms against these conditions alongside their clinical benefits.

The aim of this study was to perform a systematic review of the literature followed by a meta-analysis about the efficacy of photodynamic therapy (PDT) on the microorganisms responsible for dental caries. The research question and the keywords were constructed according to the PICO strategy. The article search was done in Embase, Lilacs, Scielo, Medline, Scopus, Cochrane Library, Web of Science, Science Direct, and Pubmed databases. Randomized clinical trials and in vitro studies were selected in the review. The study was conducted according the PRISMA guideline for systematic review. A total of 34 articles were included in the qualitative analysis and four articles were divided into two subgroups to perform the meta-analysis. Few studies have achieved an effective microbial reduction in microorganisms associated with the pathogenesis of dental caries. The results highlight that there is no consensus about the study protocols for PDT against cariogenic microorganisms, although the results showed the PDT could be a good alternative for the treatment of dental caries.

Drug delivery systems (DDS) can be designed to enrich the pharmacological and therapeutic properties of several drugs. Many of the initial obstacles that impeded the clinical applications of conventional DDS have been overcome with nanotechnology-based DDS, especially those formed by chitosan (CS). CS is a linear polysaccharide obtained by the deacetylation of chitin, which has potential properties such as biocompatibility, hydrophilicity, biodegradability, non-toxicity, high bioavailability, simplicity of modification, aqueous solubility, and excellent chemical resistance. Furthermore, CS can prepare several DDS as films, gels, nanoparticles, and microparticles to improve delivery of drugs, such as photosensitizers (PS). Thus, CS-based DDS are broadly investigated for photodynamic therapy (PDT) of cancer and fungal and bacterial diseases. In PDT, a PS is activated by light of a specific wavelength, which provokes selective damage to the target tissue and its surrounding vasculature, but most PS have low water solubility and cutaneous photosensitivity impairing the clinical use of PDT. Based on this, the application of nanotechnology using chitosan-based DDS in PDT may offer great possibilities in the treatment of diseases. Therefore, this review presents numerous applications of chitosan-based DDS in order to improve the PDT for cancer and fungal and bacterial diseases.