Beyond fluorescence-guided resection: 5-ALA-based glioblastoma therapies.

Glioblastoma is the most common primary malignant brain tumor. Despite advances in multimodal concepts over the last decades, prognosis remains poor. Treatment of patients with glioblastoma remains a considerable challenge due to the infiltrative nature of the tumor, rapid growth rates, and tumor heterogeneity. Standard therapy consists of maximally safe microsurgical resection followed by adjuvant radio- and chemotherapy with temozolomide. In recent years, local therapies have been extensively investigated in experimental as well as translational levels. External stimuli-responsive therapies such as Photodynamic Therapy (PDT), Sonodynamic Therapy (SDT) and Radiodynamic Therapy (RDT) can induce cell death mechanisms via generation of reactive oxygen species (ROS) after administration of five-aminolevulinic acid (5-ALA), which induces the formation of sensitizing porphyrins within tumor tissue. Preliminary data from clinical trials are available. The aim of this review is to summarize the status of such therapeutic approaches as an adjunct to current standard therapy in glioblastoma.

Influence of Passive Ultrasonic Irrigation of the Photosensitizer Used in Photodynamic Therapy on Microbial Reduction in the Root Canal System: An in Vitro Study.

Introduction: The success of endodontic treatment is based on microbial reduction promoted by the interaction of chemical and mechanical procedures. Photodynamic therapy (PDT) is used as an adjunct to conventional treatment, with significant microbial reduction. This study aimed to evaluate the influence of passive ultrasonic irrigation (PUI) of the photosensitizer (PS) used in PDT on microbial reduction in the root canal system. Materials and Methods: Forty-five mesiobuccal root canals from extracted human mandibular molars that were inoculated with standard strains of Enterococcus faecalis, Candida albicans, and Streptococcus mutans for 21 days were selected. The root canals were prepared using the ProTaper Next system and randomly divided into 3 groups (n=15): 1) PDT: PDT alone; 2) PUI+PDT: PUI followed by PDT; and 3) PUI/PS+PDT: PUI of the PS followed by PDT. Microbiological samples were collected from the canals before and after using the protocols described above. The data were analyzed by analysis of variance (Tukey's test) at a significance level of 5%. Results: Microbial counts before PDT, PUI+PDT, and PUI/PS+PDT did not differ significantly (P>0.05), showing methodological standardization in the microbial contamination of the root canal system. There was a significant reduction in microbial counts after PDT (61.05%), PUI+PDT (65.04%), and PUI/PS+PDT (68.58%) (P<0.01), but with no statistically significant difference between the three groups (P>0.05). Conclusion: Based on the present findings, it was concluded that the combination of PUI with PDT or PS activation did not influence microbial reduction achieved by PDT alone.

Efficacy of methylene blue-mediated antimicrobial photodynamic therapy on clinical and radiographic outcomes among patients with periodontal diseases: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This study aimed to assess the influence of methylene blue (MB)-mediated adjunctive antimicrobial photodynamic therapy (aPDT) when compared to conventional mechanical debridement (MD) alone on periodontal clinical and radiographic outcomes among periodontitis patients. METHODS: Randomized clinical trials (RCTs) were incorporated by conducting an electronic search in Web of Science, Scopus, and PubMed for articles published in English up to August 2023 to address the following focused question based on the PICO format: "Whether the application of MB-mediated aPDT as an adjunctive to MD (Intervention) leads to improved periodontal clinical and/or radiographic outcomes (Outcome) among participants with and without periodontal diseases (Population) as compared to MD alone (Conparison)". The risk of bias (RoB) of the included studies was assessed using the modified Jadad scale. A meta-analysis was conducted, and it included the presentation of the standard mean difference (SMD) along with a 95 % confidence interval (CI). RESULTS: In total, 11 studies were included in this systematic review and meta-analysis. The meta-analysis demonstrated statistically significant improvements in periodontal plaque index (SMD: -0.72 % [95 % CI: -0.99 % to -0.45 %]; p<0.00001), probing depth (SMD: -0.38 % [95 % CI: -0.57 % to -0.19 %; p<0.00001), and bleeding on probing (SMD: -0.44 % [95 % CI: -0.68 % to -0.20 %]; p = 0.0003) scores at the final follow-up visit after the application of MB-mediated aPDT in comparison with MD alone. Nevertheless, there was no statistically significant difference was observed in periodontal clinical attachment level values (SMD: -0.01 % [95 % CI: -0.21 % to 0.19 %]; p = 0.95) between the control group and the experimental group. Six studies achieved a low RoB, five were rated as having medium RoB, while no study received a high RoB. CONCLUSION: MB-mediated aPDT, when used as an adjunct to conventional MD contributes to the improvement of periodontal clinical outcomes including PI, PD, and BOP in patients with periodontitis.

Effect of antibacterial photodynamic therapy with chitosan nanoparticles on Aggregatibacter actinomycetemcomitans.

BACKGROUND: This study aimed to assess the effect of antibacterial photodynamic therapy (aPDT) with chitosan nanoparticles on Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) in the culture medium. MATERIALS AND METHODS: In this in vitro, experimental study, chitosan nanoparticles (CHNPs) containing indocyanine green (ICG) were first synthesized and characterized. A. actinomycetemcomitans was cultured on trypticase soy agar. The culture media containing A. actinomycetemcomitans were randomly subjected to the following six decontamination protocols: negative control subjected to sterile phosphate buffered saline (PBS) for 5 min, positive control exposed to 0.2 % chlorhexidine (CHX) for 5 min, exposure to 0.25 mg/mL ICG in the dark at 37 °C for 5 min, aPDT with 0.25 mg/mL ICG and diode laser (808 nm, 250 mW, 14.94 J/cm2, 30 s, 1 mm distance, 8 mm tip diameter), exposure to CHNPs containing 0.25 mg/mL ICG in the dark at 37 °C for 5 min, and aPDT with CHNPs containing 0.25 mg/mL ICG and diode laser. The number of colonies was counted, and analyzed by one-way ANOVA and Tamhane test (alpha=0.050). RESULTS: Antimicrobial PDT with CHNPs, and CHX groups comparably showed the highest decontamination efficacy (P = 0.000). CONCLUSION: The results showed optimal efficacy of aPDT with CHNPs containing 0.25 mg/mL ICG and 808 nm diode laser for reduction of A. actinomycetemcomitans colony count. Thus, aPDT appears to be as effective as CHX, but with fewer adverse effects.

Adhesive Bond Strength of Restorative Materials to Caries-Affected Dentin Treated with Antimicrobial Photodynamic Therapy: A Systematic Review and Meta-Analysis.

Objective: This systematic review aimed to evaluate the adhesive bond strength of restorative materials to caries-affected dentin (CAD) treated with antimicrobial photodynamic therapy (aPDT) in comparison with conventional chemical disinfectants. Methods: Three databases, including the Web of Science, Scopus, and PubMed, were searched to address the focused question: "What is the effect of aPDT compared to conventional chemical disinfection techniques on the adhesive bond strength of restorative materials to CAD?." Search keywords included "dentin*" "adhes bond*" "caries-affected dentin" "photodynamic "photochemotherapy" "photosensitizing agent" "phototherapy" "photoradiation" "laser" "light activated" "photoactivated." A fixed-effects model was used in each meta-analysis and the inverse variance was used to calculate the standard mean difference (SMD). For evaluating the statistical heterogeneity, the Cochrane's Q test and the I2 statistics were used. The risk of bias was evaluated based on the Cochrane Collaboration's tool. Results: Fourteen studies were included in the qualitative as well as quantitative analysis. The results of the meta-analyses exhibited an SMD of 2.38% [95% confidence interval (CI): 2.03-2.73; p < 0.00001], indicating a statistically significant difference in the shear bond strength scores between the tested group (samples treated with aPDT) and the control group (i.e., favoring the sound dentin and/or conventional chemical disinfectants). Contrarily, an SMD of -1.46% (95% CI: -2.04 to -0.88; p < 0.00001) and -0.37% (95% CI: -0.70 to -0.03; p = 0.03) was observed, indicating a statistically significant difference in the microtensile bond strength (µTBS), as well as microleakage scores between the tested group (favoring the samples treated with aPDT) and the control group (i.e., sound dentin and/or conventional chemical disinfectants). Conclusions: Adhesive bond strength of restorative materials to CAD treated with conventional chemical disinfectants showed superior outcomes compared to photodynamic therapy (aPDT).

Morphological changes and viability of Streptococcus mutans biofilm treated with erythrosine: A confocal laser scanning microscopy analysis.

Antimicrobial photodynamic therapy (a-PDT) is a modality that aims to induce microorganisms through visible light, a photosensitizer, and molecular oxygen. This therapy has shown promising results in controlling cariogenic biofilm in vitro and in vivo counterparts. This study investigated bacterial viability and morphological characterization of Streptococcus mutans mature biofilms after combination of erythrosine and a high potency dental curing light. Biofilms were formed on saliva-coated hydroxyapatite disks in batch culture. The samples were performed in triplicates. Fresh medium was replaced daily for five days and treated using 40 µM of E activated by HL 288 J/cm2 and total dose of 226 J at 1200 mW/cm2. Phosphate buffer saline and 0.12% of chlorhexidine were used as negative and positive control, respectively. After treatment, biofilms were assessed for microbial viability and morphological characterization by means of bio-volume and thickness. COMSTAT software was used for image analysis. Data were analyzed using two-way ANOVA followed by Tukey test with significance level 5%. The application of a-PDT and CHX treatments decreased S. mutans bacterial viability. The image analysis showed more red cells on biofilms when compared to other groups, demonstrating photobacterial killing. Erythrosine irradiated with a high potency curing light can potentially act as an antimicrobial tool in the treatment of cariogenic biofilms. The morphology and viability of microorganisms were impacted after treatment. Treatment with photodynamic therapy may be able to reduce the bio-volume and viability of bacteria present in biofilms. CLINICAL RELEVANCE AND RESEARCH HIGHLIGHTS: The use of the a-PDT technique has been applied in dentistry with satisfactory results. Some applications of this technique are in stomatology and endodontics. In the present study, we sought to understand the use of photodynamic therapy in the control of biofilm and the results found are compatible with the objective of microbiological control proposed by this technique, thus raising the alert for future studies in vivo using the combination of a-PDT with erythrosine, since they are easily accessible materials for the dental surgeon and can be applied in clinical practice.

Evaluation of unilateral corneal collagen cross-linking on fellow untreated eyes of patients with keratoconus / A avaliação da reticulação unilateral do colágeno corneano em olhos não tratados de pacientes com ceratocone

ABSTRACT Purpose: This study aimed to examine the effects of unilateral corneal collagen cross-linking treatment on visual acuity and the topographic findings of the fellow untreated eye of patients who had bilateral progressive keratoconus. Methods: Patients with progressive keratoconus who underwent cross-linking treatment were screened retrospectively. A total of 188 untreated eyes of 188 patients whose eyes were treated unilaterally with either standard or accelerated cross-linking and refused cross-linking procedure for the fellow eye were included. Visual acuity and topographic findings of the fellow untreated eyes were obtained preoperatively and postoperatively at the 1st, 3rd, 6th, 12th, 24th, 30th, and 36th months. Results: The change over time of variables examined was similar in the untreated eyes of patients who received standard and accelerated cross-linking methods (p>0.05). At the 12th month, 136 (95.8%) untreated eyes were stable according to progression criteria. Only 4 (8%) eyes were progressive at the 24th month. No progression was observed in any of the 16 patients with a 36-month follow up. Conclusions: The results showed that the fellow untreated eyes of patients with bilateral progressive keratoconus did not have significant progression rates after unilateral cross-linking treatment.

RESUMO Objetivo: Examinar os efeitos do tratamento de reticulação unilateral do colágeno corneano na acuidade visual e os achados topográficos em olhos não tratados de pacientes com ceratocone progressivo bilateral. Métodos: Foram rastreados retrospectivamente pacientes com ceratocone progressivo submetidos a tratamento de reticulação. Foram incluídos no estudo 188 olhos não tratados de 188 pacientes tratado unilateralmente com reticulação padrão ou acelerada e que recusaram o procedimento de reticulação no outro olho. A acuidade visual e os achados topográficos dos olhos não tratados foram obtidos no pré- e pós-operatório no 1º, 3º, 6º, 12º, 24º, 30º e 36º mês. Resultados: As alterações ao longo do tempo foram semelhantes para as variáveis examinadas nos olhos não tratados de pacientes tratados com métodos de reticulação padrão e acelerado (p>0,05). No 12º mês, 136 olhos não tratados (95,8%) estavam estáveis, de acordo com os critérios de progressão. Apenas quatro olhos (8%) mostraram progressão no 24º mês. Nenhuma progressão foi observada nos 16 pacientes que tiveram um acompanhamento de 36 meses. Conclusões: O estudo mostrou que os olhos não tratados de pacientes com ceratocone progressivo bilateral não apresentaram taxas de progressão significativas após o tratamento unilateral com reticulação.

Emerging role of photodynamic therapy as an adjunct to nonsurgical periodontal therapy on periodontal status and glycemic control in patients with type 2 diabetes: A clinical study.

Background: Periodontal disease is considered to be the sixth most common complication of diabetes mellitus (DM). Antibiotics (systemic and local) enhance the outcome of conventional mechanical debridement but frequent use of antimicrobials may develop resistance to microorganisms. To overcome this complicacy, the current study assessed the effectiveness of photodynamic therapy (PDT) in chronic periodontitis patients with type 2 diabetes when used as a combination therapy to standard periodontal therapy by assessing the various clinical and glycemic parameters. Materials and Methods: A total of 16 known cases of chronic Periodontitis patients who were suffering from type 2 DM were allocated into two groups. The test group (n = 8) was treated with standard scaling and root planing (SRP) along with PDT while the control group was treated with SRP alone. Various clinical parameters assessed were plaque index, gingival index, pocket probing depth, clinical attachment level, and Glycated hemoglobin level at baseline and 90 days after therapy. Results: At the end of the study, both the groups showed improvements with regard to all clinical and glycemic parameters compared to baseline. However, the test group presented statistically significant favorable results (all P < 0.05). Conclusion: Conventional periodontal treatment aided with PDT proved to be a beneficial therapeutic measure and effective alternative in patients with chronic periodontitis with diabetes when compared with standard periodontal therapy alone.

Ocorrência de carcinoma espinocelular labial não melanocítico em usuários crônicos de hidroclorotiazida / Occurrence of non-melanoma labial squamous cell carcinoma in chronic users of hydrochlorothiazide

Diversos autores desenvolveram estudos acerca da potencial associação entre a etiocarcinogênese do carcinoma espinocelular não melanocítico (CECNM) labial e o uso crônico da hidroclorotiazida (HCTZ). Objetivo: A atual revisão objetivou investigar a relação do diurético HCTZ e o risco de CECNM labial. Métodos: Realizou-se uma revisão de literatura nas bases de dados LILACS, PUBMED/MEDLINE e Periódico CAPES, em que foram incluídos artigos em inglês, português e francês, publicados no período de 2017 a 2022. Foram propostos 60 documentos e, dentre esses, 30 foram selecionados para compor a amostra no estudo. Resultados: Foi evidenciada uma relação entre o uso da HCTZ e a ocorrência de CENM com relação dose cumulativa devido às alterações provocadas pelo fármaco, no entanto, em virtude da heterogeneidade de desenhos metodológicos e concentração dos estudos em populações semelhantes, existem limitações quanto à confiabilidade dessas informações. Conclusão: Identificou-se uma desproporção entre a ocorrência e relevância do CENM e a produção científica vigente, demonstrando a necessidade de estudos com metodologias padronizadas que abranjam diferentes especificidades socioeconômicas e demográficas.(AU)

Several authors have developed studies about a potential association between the etiocarcinogenesis of non-melanocytic lip squamous cell carcinoma (NMSCC) and the chronic use of hydrochlorothiazide (HCTZ). Objective: The current study aimed to investigate the relation between the diuretic HCTZ and the risk of lip NMSCC. Methods: A literature review was carried out in the LILACS, PUBMED/MEDLINE and CAPES Periodical databases, which included articles in English, Portuguese and French, published between 2017 and 2022. Sixty documents were collected and, among these, 30 were selected to compose the sample in the study. Results: There was evidence of a relationship between the use of HCTZ and the occurrence of MSCC with a cumulative dose relationship due to changes caused by the drug, however, because of the heterogeneity of methodological designs and concentration of studies in similar populations, there are limitations regarding the reliability of this information. Conclusion: A disproportion between the occurrence and relevance of the NMSCC and the current scientific production was identified, demonstrating the need for studies with standardized methodologies that cover different demographic socioeconomic specificities.(AU)

Antibacterial effectiveness of photo-sonodynamic treatment by methylene blue-incorporated poly(D, L-lactide-co-glycolide) acid nanoparticles to disinfect root canals.

AIM: This in-vitro investigation aimed to assess the antibacterial effectiveness of photo-sonodynamic treatment using methylene blue (MTB)-incorporated poly(D, L-Lactide-Co-Glycolide) acid (PLGA)-nanoparticles for the disinfection of root canals. METHODS: The synthesis of PLGA nanoparticles was achieved using a solvent displacement technique. The morphological and spectral characterization of the formulated PLGA nanoparticles were carried out using scanning electron microscopy (SEM) and Transformed-Fourier infrared spectroscopy (TFIR), respectively. One hundred human premolar teeth were sterilized and then their root canals were infected with Enterococcus faecalis (E. faecalis). Later, the bacterial viability evaluation of the following 5 research groups was conducted: (a) G-1: specimens treated with a diode laser; (b) G-2: specimens treated with antimicrobial photodynamic therapy (aPDT) and 50 µg/mL of MTB-incorporated PLGA nanoparticles; (c) G-3: specimens treated with ultrasound (US); (d) G-4: specimens treated with US and 50 µg/mL of MTB-incorporated PLGA nanoparticles; and (e) G-5: control group consisting of specimens that did not undergo any treatment. RESULTS: Under SEM, the nanoparticles exhibited a uniform spherical shape and were around 100 nm. The formulated nanoparticles' size was validated through zeta potential analysis utilizing dynamic light scattering (DLS). The TFIR images of both PLGA nanoparticles and MTB-incorporated PLGA nanoparticles exhibited absorption bands ranging from around 1000 to 1200/cm and nearly from 1500 to 1750/cm. The G-5 samples (control group) demonstrated the greatest viability against E. faecalis, followed by G-3 (US-conditions specimens), G-1 (diode laser-conditioned specimens), G-2 (aPDT + MTB-incorporated PLGA-nanoparticles-conditioned specimens), and G-5 (US + MTB-incorporated PLGA-nanoparticles-conditioned specimens). Significant statistical differences (p < 0.05) were observed among all research groups, including both the experimental groups and control group. CONCLUSION: The combination of US via MTB-incorporated PLGA nanoparticles exhibited the most effective eradication of E. faecalis, suggestive of a promising therapeutic modality against E. faecalis for disinfecting root canals with complex and challenging anatomy.

Efficacy of methylene blue and curcumin mediated antimicrobial photodynamic therapy in the treatment of indirect pulp capping in permanent molar teeth.

PURPOSE: This study aimed to evaluate the adhesive bond strength and antibacterial efficacy of methylene blue (MB)-mediated antimicrobial photodynamic therapy (aPDT) and curcumin (CUR)-mediated aPDT versus the conventional disinfectants, such as chlorhexidine gluconate (CHX) gel and sodium hypochlorite (NaOCl), for indirect pulp capping (IPC) treatment of permanent molars. METHODS: One Hundred grossly carious human permanent molars were collected through non-traumatic extraction. All specimens were embedded in polyvinyl cross-sections to the cemento-enamel junction. The cavity preparation was conducted by grinding the samples using silicon carbide discs. After culturing Streptococcus mutans (S. mutans), a 10 µL of S. mutans suspension (106 colony forming units/mL) was transferred in each tooth cavity and anaerobically incubated for 48 h at 37 °C. All specimens were randomly divided into 5 groups: Group-I: samples treated IPC; Group-II: samples treated with 2% CHX gel; Group-III: samples treated with 6% NaOCl; Group-IV: irradiation of prepared cavity with MB-mediated aPDT; and Group-V: irradiation of prepared cavity with CUR-mediated aPDT. After disinfection methods, the universal adhesive was used, and all specimens were restored using giomer. Eventually, confocal laser scanning microscopy, shear bond strength (SBS), micro-tensile bond strength (µTBS), four-point bending strength (4P-BS) analyses were performed, and the data were analyzed statistically. RESULTS: At baseline, the highest SBS (48.8 ± 6.5 MPa), µTBS (54.3 ± 3.9 MPa), and 4P-BS (123 ± 32 MPa) scores were demonstrated by the samples treated with MB-mediated aPDT. However, after 12 months of storage, the highest SBS (42.3 ± 3.9 MPa) and µTBS (45.2 ± 6.6 MPa) scores were shown by samples treated with MB-mediated aPDT, while CUR-mediated aPDT treated samples demonstrated the highest 4P-BS scores (70 ± 18 MPa). Moreover, the highest antibacterial activity against S. mutans was shown by the samples treated with MB-mediated aPDT. CONCLUSIONS: The application of aPDT, especially MB-mediated, demonstrated superior SBS, µTBS, and 4P-BS values as well as antibacterial activity against S. mutans as compared to 2% CHX gel and 6% NaOCl as cavity disinfectants for IPC treatment of permanent molars.

Effect of photodynamic therapy according to differences in photosensitizers on Staphylococcus aureus biofilm on titanium.

PURPOSE: This study aimed to evaluate the antimicrobial effect of photodynamic therapy (PDT) against Staphylococcus aureus biofilm on a titanium surface and to compare the differences in the effect of PDT using toluidine blue O (TBO) and methylene blue (MB) as a photosensitizer. METHODS: The bacterial strain S. aureus ATCC 25,923 was used. Sandblasted and acid-etched (SLA) disks were divided into the following six groups: phosphate buffer saline (PBS), TBO, MB, PBS with laser (PBS + L), TBO with laser (TBO + L), and MB with laser (MB + L). The laser group samples were irradiated by a cold diode laser for 60 s. After treatment, the number of surviving bacteria was calculated by counting the colony-forming units (CFUs) and confocal laser scanning microscopy (CLSM) was applied to observe the bacteria on the disk surface. RESULTS: The TBO + L and MB + L groups showed significantly lower CFU/ml than the other groups (p < 0.01). The TBO + L group showed significantly lower CFU/ml than the MB + L group (p = 0.032). There was no significant difference between the PBS, TBO, MB, and PBS + L groups. Within the limitations of this in vitro study, PDT with TBO and MB can effectively reduce S. aureus biofilm on SLA titanium surfaces. TBO is more effective than MB as a photosensitizer. PDT with TBO may be applied to the treatment of peri­implant disease in the future.

A rare case of refractory facial phaeohyphomycosis caused by Cladosporium halotolerans successfully treated with aminolevulinic acid photodynamic therapy.

A 55-year-old female presented with a gradually enlarged red plaque and ulceration on the right side of her nose, face and suborbital region for ten years. The histopathologic features indicated infectious granuloma. The results of the fungal culture of the tissue and DNA sequencing identified as Cladosporium halotolerans infection. The patient was diagnosed with phaeohyphomycosis due to Cladosporium halotolerans. In this case, it was unsuitable for surgical treatment since the lesion was located periorbital. Furthermore, the patient had a poor response to oral itraconazole (400 mg/d) for 9 months. Therefore, ALA-PDT was added to the treatment regimen. The patient received ALA-PDT irradiation 5 times at 2-week intervals and achieved significant clinical remission. We believe that ALA-PDT may be an effective and safe adjuvant therapy.

Phytochemical Profile and In Vitro Antioxidant and Photobiological Properties of Different Extracts from Prangos ferulacea Lindl.

Interesting photobiological properties have been demonstrated for some Cachrys species, including C. libanotis L., C. sicula L., and C. pungens Jan. The present study was designed to assess the photocytotoxic activity of Prangos ferulacea Lindl. (synonym of C. ferulacea (L.) Calest.). This plant was previously considered a Cachrys species but, at present, it is part of the Prangos genus. P. ferulacea is an orophilous plant present in the eastern Mediterranean and in western Asia. Three different extraction techniques were utilized. Obtained extracts were compared both for their phytochemical content and for their photobiological properties on human melanoma cells irradiated with UVA light. The apoptotic responses, together with the antioxidant activity, were also assessed. P. ferulacea extracts were able to affect cell viability in a concentration-dependent manner, with the sample obtained through supercritical CO2 extraction showing the highest activity (IC50 = 4.91 µg/mL). This research points out the interesting content in the photoactive compounds of this species, namely furanocoumarins, and could provide a starting point for further studies aimed at finding new photosensitizing agents useful in cancer photochemotherapy.

Clinical efficacy of 5-aminolevulinic acid-mediated photodynamic therapy versus topical antifungal agent and surgical excision for the treatment of hyperplastic candidiasis.

BACKGROUND: Hyperplastic candidiasis (HC) is a chronic infection of oral mucosa caused by Candida. Owing to its potential for malignant transformation, its intervention requires attention. Conventional surgical resection might lead to irreversible damage and impact the patient's quality of life. Hence, this study aimed to evaluate the clinical efficacy of 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy (PDT) alone and in combination with topical antifungal therapy (i.e., nystatin [combination therapy]) in comparison with nystatin and surgical resection for the treatment of HC. METHODS: Forty subjects with clinical and histopathological diagnoses of HC were included in the study. Four study groups, with 10 participants each, were formed as follows: Group-I - receiving antifungal agent [nystatin]; Group-II - receiving surgical resection; Group-III - receiving PDT; and Group-IV - receiving 5-ALA-mediated PDT and nystatin [combination therapy]. Salivary and mucosal samples were collected for the quantification of Candida albicans and the treatment responses to different interventions were recorded at week-4, week-6, and week-8 after finishing therapies. RESULTS: At the 3rd follow-up (i.e., at end of the 8th week after the interventions), complete improvement in 3 (30%), 2 (20%), 1 (10%), and 5 (50%) patients in group-I, group-II, group-III, and group-IV, respectively was observed. A statistically significant difference was obtained when the intervention responses were compared at week-4 (p<0.01), week-6 (p<0.01), and week-8 (p<0.0001) follow-ups in group-I, group-II, and group-IV subjects. At the 8-week follow-up regarding the salivary and mucosal samples, the lowest colony-forming units/milliliter score of C. albicans was observed in group-IV subjects. CONCLUSION: The application of 5-ALA-mediated PDT in combination with nystatin gel possesses the potential as a well-tolerated and safe therapeutic modality for the treatment of patients with HC.

Efficacy of 5-aminolevulinic acid-mediated photodynamic therapy in patients with nicotine stomatitis.

AIM: This study aimed to treat smoker's palate (SP) using 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy (PDT). METHODS: A total of 24 patients with SP were divided into two groups: group-I (test group; n = 12); and group-II (control group; n = 12). Group-I patients were treated with 5-ALA-mediated PDT, while group-II patients were advised to cease the smoking habit during the entire duration of the study and later. PDT was repeated on days 3, 7, and 14 (i.e., a total of four sittings including day 0 [baseline]). Later, the participants were called for follow-up after week-4 (1st follow-up), week-6 (2nd follow-up), and week-8 (3rd follow-up) after the completion of the treatment. The SPSS version 22.0 was used for data analysis. RESULTS: Group-I patients showed a statistically significant improvement when all three time points were assessed (p < 0.0001). Similarly, the same trend was observed in the group-II participants (p < 0.001), however, the difference between both groups (i.e., group-I [test group] and group-II [control group]) was larger. CONCLUSION: The findings of this clinical trial indicated a promising and satisfactory decrease in the clinical features of the smoker's palate without any adverse impacts utilizing 5-aminolevulinic acid-mediated photodynamic therapy. Hence, 5-ALA-mediated PDT appeared to be a promising treatment option together with smoking cessation.

Chlorin-based photosensitizer under blue or red-light irradiation against multi-species biofilms related to periodontitis.

In our previous study, Chlorin-e6 (Ce6) demonstrated a significant reduction of microorganisms' viability against single-species biofilm related to periodontitis once irradiated by red light (660 nm). Also, higher bacteria elimination was observed under blue light (450 nm) irradiation. However, the use of blue light irradiation of Ce6 for antimicrobial administration is poorly explored. This study evaluated the effect of chlorin-e6-mediated antimicrobial photodynamic therapy (aPDT) using different wavelengths (450 or 660 nm) against multi-species biofilms related to periodontitis. Streptococcus oralis, Fusobacterium nucleatum, Porphyromonas gingivalis, and Aggregatibacter actinomycetemcomitans composed the mature biofilm developed under proper conditions for five days. aPDT was performed using different concentrations of Ce6 (100 and 200 µM), wavelengths (450 or 660 nm), and comparisons were made after qPCR assay and confocal laser scanning microscopy (CLSM) analysis. The greatest bacterial elimination was observed in the groups where Ce6 was used with blue light, for S. orallis (2.05 Log10 GeQ mL-1, p < 0.0001) and P. gingivalis (1.4 Log10 GeQ mL-1, p < 0.0001), aPDT with red light showed significant bacteria reduction only for S. orallis. aPDT with blue light demonstrated statistically higher elimination in comparison with aPDT with red light. The aPDT did not show a statistically significant effect when tested against A. actinomycetemcomitans and F. nucleatum (p=0.776 and 0.988, respectively). The aPDT using blue light showed a promising higher photobiological effect, encouraging researchers to consider it in the irradiation of Ce6 for further investigations.

New tricyclic systems as photosensitizers towards triple negative breast cancer cells.

Nineteen pyrrolo[1,2-h][1,7]naphthyridinones and pyrido[2,3-c]pyrrolo[1,2-a]azepinones were synthesized as new tricyclic systems in which the pyridine ring is annelated to the 6,7-dihydroindolizin-8(5H)-one and 5,6,7,8-tetrahydro-9H-pyrrole[1,2-a]azepine-9-one moieties to obtain potential photosensitizing agents. They were tested for their photoantiproliferative activity on a triple-negative breast cancer cell line, MDA-MB-231, in the dark and under UVA light (2.0 J/cm2). We demonstrated that their toxicity, only when exposed to light, was primarily due to the generation of reactive oxygen species while their photodegradation products were not responsible for their activity. The most active compounds exhibited photocytotoxicity with IC50 values at low micromolar level inducing a decrease in the intracellular content of thiol, thus triggering cancer cell death through apoptosis. All the pyridone derivatives revealed to be pure photosensitizers with preferential photocytotoxic activity towards cancerous over healthy cells. Altogether, the results obtained confirm pyrrolo[1,2-h][1,7]naphthyridinones and pyrido[2,3-c]pyrrolo[1,2-a]azepinones as promising photosensitisers against triple-negative breast cancer.

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.

Insight on pyrimido[5,4-g]indolizine and pyrimido[4,5-c]pyrrolo[1,2-a]azepine systems as promising photosensitizers on malignant cells.

Searching for new small molecules as photosensitizing agents, we have developed a class of twenty-five pyrimido[5,4-g]indolizine and pyrimido[4,5-c]pyrrolo[1,2-a]azepines with a good substitution pattern defining a versatile synthetic pathway to approach the title ring system. All compounds were evaluated for their photocytotoxicity on a triple negative human breast cancer cell line (MDA-MB-231) in the dark and under UVA light (2.0 J/cm2). The most effective compounds exhibited a photoantiproliferative activity with IC50 values up to nanomolar ranges. Interestingly, these new developed compounds showed high selectivity towards cancerous cells with respect to non-cancerous ones. Moreover, four representative derivatives demonstrated to be phototoxic also against an additional human HER2 positive breast cancer cell line (HCC1954), and against the HER2 positive vesical cancer cell line (T24) harboring Hras mutation. Mechanistic studies performed in triple negative MDA-MB-231 cancer cells revealed the ability of the compounds to increase reactive oxygen species (ROS) production and to induce a thiol redox stress, thus triggering cancer cell death through apoptosis. Apoptotic cell death was also induced in highly aggressive and metastatic HER2 positive Hras mutated T24-treated bladder cancer cells. Overall, our data confirm that these new small photosensitizing agents may represent very promising candidates for phototherapy application against highly aggressive and resistant cancers.