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1.
J Evid Based Dent Pract ; 24(2): 101899, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38821659

RESUMO

OBJECTIVES: Despite phototherapy (in the form of photodynamic therapy (PDT)-mediated oxidative stress) being utilized in the management of oral potentially malignant disorders (OPMDs), the evidence of certainty remains unclear. Hence, this systematic review and meta-analysis (PROSPERO # CRD42021218748) is aimed to evaluate the clinical efficacy of PDT-induced oxidative stress in OPMDs METHODS: PubMed, Embase, Web of Science, Scopus, and Cochrane Library databases were searched without restriction of language or year of publication. In addition, gray literature was searched and a manual search was performed. Two independent reviewers screened all the studies, assessing data extraction, risk of bias and certainty of evidence. A narrative synthesis was carried out. For the meta-analysis, random effects were considered to determine the prevalence of a total and a partial remission (PR) of oral potentially malignant disorders (OPMDs). The certainty of evidence was explored using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. RESULTS: Twenty-three studies were included in the qualitative and quantitative syntheses. A total of 880 patients were included (564 males; 218 females) with an age range between 24 and 89-years-old. The results showed the prevalence of the total and partial remissions respectively for the following OPMLs: actinic cheilitis (AC): 69.9% and 2.4%; oral leukoplakia (OL): 44% and 36.9%; oral verrucous hyperplasia (OVH): 98.5%; oral erythroleukoplakia (OEL): 92.1% and 7.9%. The prevalence of no remission of OL was 18.8%. CONCLUSIONS: PDT demonstrated significant results in clinical remission of OPMDs and most of the eligible studies have shown a total or a partial remission of the included lesions, but at a low or a very low certainty of evidence. Hence, further clinical studies with robust methodology are warranted to offer further validated data. Also, further evidence is required to understand further the mechanism of PDT-induced oxidative stress.


Assuntos
Neoplasias Bucais , Fotoquimioterapia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Queilite/tratamento farmacológico , Neoplasias Bucais/tratamento farmacológico , Estresse Oxidativo , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Lesões Pré-Cancerosas/tratamento farmacológico , Resultado do Tratamento , Adulto , Pessoa de Meia-Idade
2.
Rev. estomatol. Hered ; 34(1): 77-ene.-mar. 2024.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1565547

RESUMO

RESUMEN La desinfección se consigue mediante procedimientos como la instrumentación, la irrigación y la medicación intraconducto; sin embargo, estos no son suficientes, ya que diversos estudios han reportado al E. faecalis como uno de los microorganismos persistentes con mayor prevalencia en tratamientos de conductos que no han conseguido la curación de los tejidos periapicales. Se ha tratado de mejorar los protocolos de desinfección incluyendo diferentes herramientas tecnológicas como en el caso de la terapia fotodinámica, la cual utiliza una fuente de luz y sustancias fotosensibilizantes que favorecen el proceso de eliminación de las bacterias remanentes dentro del sistema de conductos radiculares. La presente revisión de literatura científica profundiza en la importancia clínica de la terapia fotodinámica y su efecto en la desinfección e inhibición del E. faecalis dentro del sistema de conductos, lo cual se ha vuelto una pieza clave para el éxito del tratamiento endodóntico.


ABSTRACT Disinfection is achieved through procedures such as instrumentation, irrigation, and intra-canal medication; however, these are not enough since several studies have reported E. faecalis as one of the most prevalent persistent microorganisms in root canal treatments that have not achieved healing of the periapical tissues. Efforts have been made to improve disinfection protocols by including different technological tools, as in the case of photodynamic therapy, which uses a light source and photosensitizing substances that favor the process of elimination of the remaining bacteria within the root canal system. The present review of scientific literature delves into the clinical importance of photodynamic therapy and its effect on the disinfection and inhibition of E. faecalis within the root canal system, which has become a key element for the success of endodontic treatment.


RESUMO A desinfeção é conseguida através de procedimentos como a instrumentação, a irrigação e a medicação intracanal; no entanto, isto não é suficiente, uma vez que vários estudos relataram a E. faecalis como um dos microrganismos persistentes mais prevalentes nos canais radiculares que não conseguiram cicatrizar os tecidos periapicais. Têm sido feitos esforços para melhorar os protocolos de desinfeção através da inclusão de diferentes ferramentas tecnológicas, como a terapia fotodinâmica, que utiliza uma fonte de luz e substâncias fotossensibilizadoras que favorecem o processo de eliminação das bactérias remanescentes no sistema de canais radiculares. Esta revisão da literatura científica analisa a importância clínica da terapia fotodinâmica e o seu efeito na desinfeção e inibição da E. faecalis no interior do sistema de canais radiculares, o que se tornou um fator chave para o sucesso do tratamento endodôntico.

3.
Photochem Photobiol ; 100(1): 190-203, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37395166

RESUMO

Photodynamic therapy (PDT) has been used for various purposes, including as an antitumor resource in a noninvasive therapy with minimal side effects. Sinningia magnifica (Otto & A. Dietr.) Wiehler is a rupicolous plant found in rock crevices in Brazilian tropical forests. Initial studies indicate the presence of phenolic glycosides and anthraquinones in species of the genus Sinningia (Generiaceae family). It is known that anthraquinones are natural photosensitizers with potential PDT applications. This led us to investigate the potential compounds of S. magnifica for use as a natural photosensitizer against the melanoma (SK-MEL-103) and the prostate cancer (PC-3) cell lines in a bioguided study. Our results showed that singlet oxygen production by the 1,3-DPBF photodegradation assay greatly increased in the presence of crude extract and fractions. The biological activity evaluation showed photodynamic action against melanoma cell line SK-MEL-103 and prostate cell line PC-3. These results suggest the presence of potential photosensitizing substances, as demonstrated in this in vitro antitumor PDT study by the naphthoquinones Dunniol and 7-hydroxy-6-methoxy-α-dunnione for the first time. Naphthoquinones, anthraquinones and phenolic compounds were identified in the crude extract by UHPLC-MS/MS analysis, motivating us to continue with the bioguided phytochemical study aiming to discover more photochemically bioactive substances in Gesneriaceae plants.


Assuntos
Melanoma , Naftoquinonas , Fotoquimioterapia , Humanos , Espectrometria de Massas em Tandem , Melanoma/tratamento farmacológico , Naftoquinonas/farmacologia , Naftoquinonas/química , Naftoquinonas/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Antraquinonas/farmacologia , Antraquinonas/química , Misturas Complexas
4.
Lasers Med Sci ; 38(1): 274, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37993626

RESUMO

The aim of this study was to investigate whether antimicrobial blue light (aBL) can cause the death of Aggregatibacter actinomycetemcomitans (A.a) and to determine the influence of different culture media, specifically brain heart infusion and blood agar, on bacterial survival fraction. An LED emitting at 403 ± 15 nm, with a radiant power of 1W, irradiance of 588.2 mW/cm2, and an irradiation time of 0 min, 1 min, 5 min, 10 min, 30 min, and 60 min, was used. The plates were incubated in microaerophilic conditions at 37 °C for 48 h, and the colony-forming units were counted. The photosensitizers were investigated using spectroscopy and fluorescence microscopy. There was no significant difference between the culture media (p > 0.05). However, a statistical reduction in both media was observed at 30 min (1058 J/cm2) (p < 0.05). The findings of this study suggest that aBL has the potential to kill bacteria regardless of the culture media used. Light therapy could be a promising and cost-effective strategy for preventing periodontal disease when used in combination with mechanical plaque control.


Assuntos
Anti-Infecciosos , Fotoquimioterapia , Fotoquimioterapia/métodos , Aggregatibacter actinomycetemcomitans/efeitos da radiação , Luz , Fármacos Fotossensibilizantes/farmacologia , Meios de Cultura/farmacologia
5.
Pharmaceutics ; 15(2)2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36839714

RESUMO

The increase in the antibiotic resistance of bacteria is a serious threat to public health. Photodynamic inactivation (PDI) of micro-organisms is a reliable antimicrobial therapy to treat a broad spectrum of complex infections. The development of new photosensitizers with suitable properties is a key factor to consider in the optimization of this therapy. In this sense, four corroles were designed to study how the number of cationic centers can influence the efficacy of antibacterial photodynamic treatments. First, 5,10,15-Tris(pentafluorophenyl)corrole (Co) and 5,15-bis(pentafluorophenyl)-10-(4-(trifluoromethyl)phenyl)corrole (Co-CF3) were synthesized, and then derivatized by nucleophilic aromatic substitution with 2-dimethylaminoethanol and 2-(dimethylamino)ethylamine, obtaining corroles Co-3NMe2 and Co-CF3-2NMe2, respectively. The straightforward synthetic strategy gave rise to macrocycles with different numbers of tertiary amines that can acquire positive charges in an aqueous medium by protonation at physiological pH. Spectroscopic and photodynamic studies demonstrated that their properties as chromophores and photosensitizers were unaffected, regardless of the substituent groups on the periphery. All tetrapyrrolic macrocycles were able to produce reactive oxygen species (ROS) by both photodynamic mechanisms. Uptake experiments, the level of ROS produced in vitro, and PDI treatments mediated by these compounds were assessed against clinical strains: methicillin-resistant Staphylococcus aureus and Klebsiella pneumoniae. In vitro experiments indicated that the peripheral substitution significantly affected the uptake of the photosensitizers by microbes and, consequently, the photoinactivation performance. Co-3NMe2 was the most effective in killing both Gram-positive and Gram-negative bacteria (inactivation > 99.99%). This work lays the foundations for the development of new corrole derivatives having pH-activable cationic groups and with plausible applications as effective broad-spectrum antimicrobial photosensitizers.

6.
Molecules ; 27(20)2022 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-36296441

RESUMO

Photodynamic therapy (PDT) is a noninvasive therapeutic approach that has been applied in studies for the treatment of various diseases. In this context, PDT has been suggested as a new therapy or adjuvant therapy to traditional cancer therapy. The mode of action of PDT consists of the generation of singlet oxygen (¹O2) and reactive oxygen species (ROS) through the administration of a compound called photosensitizer (PS), a light source, and molecular oxygen (3O2). This combination generates controlled photochemical reactions (photodynamic mechanisms) that produce ROS, such as singlet oxygen (¹O2), which can induce apoptosis and/or cell death induced by necrosis, degeneration of the tumor vasculature, stimulation of the antitumor immune response, and induction of inflammatory reactions in the illuminated region. However, the traditional compounds used in PDT limit its application. In this context, compounds of biotechnological origin with photosensitizing activity in association with nanotechnology are being used in PDT, aiming at its application in several types of cancer but with less toxicity toward neighboring tissues and better absorption of light for more aggressive types of cancer. In this review, we present studies involving innovatively developed PS that aimed to improve the efficiency of PDT in cancer treatment. Specifically, we focused on the clinical translation and application of PS of natural origin on cancer.


Assuntos
Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/química , Oxigênio Singlete/química , Espécies Reativas de Oxigênio/metabolismo , Neoplasias/tratamento farmacológico , Oxigênio
7.
Nanomaterials (Basel) ; 12(20)2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36296737

RESUMO

Photodynamic therapy (PDT) mediated by photosensitizers loaded in nanostructures as solid lipid nanoparticles has been pinpointed as an effective and safe treatment against different skin cancers. Amazon butters have an interesting lipid composition when it comes to forming solid lipid nanoparticles (SLN). In the present report, a new third-generation photosensitizing system consisting of aluminum-phthalocyanine associated with Amazon butter-based solid lipid nanoparticles (SLN-AlPc) is described. The SLN was developed using murumuru butter, and a monodisperse population of nanodroplets with a hydrodynamic diameter of approximately 40 nm was obtained. The study of the permeation of these AlPc did not permeate the analyzed skin, but when incorporated into the system, SLN-AlPc allowed permeation of almost 100% with 8 h of contact. It must be emphasized that SLN-AlPc was efficient for carrying aluminum-phthalocyanine photosensitizers and exhibited no toxicity in the dark. Photoactivated SLN-AlPc exhibited a 50% cytotoxicity concentration (IC50) of 19.62 nM when applied to B16-F10 monolayers, and the type of death caused by the treatment was apoptosis. The exposed phospholipid phosphatidylserine was identified, and the treatment triggered a high expression of Caspase 3. A stable Amazon butter-based SLN-AlPc formulation was developed, which exhibits strong in vitro photodynamic activity on melanoma cells.

8.
Molecules ; 27(18)2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36144496

RESUMO

In this study, we describe the semisynthesis of cost-effective photosensitizers (PSs) derived from chlorophyll a containing different substituents and using previously described methods from the literature. We compared their structures when used in photodynamic inactivation (PDI) against Staphylococcus aureus, Escherichia coli, and Candida albicans under different conditions. The PSs containing carboxylic acids and butyl groups were highly effective against S. aureus and C. albicans following our PDI protocol. Overall, our results indicate that these nature-inspired PSs are a promising alternative to selectively inactivate microorganisms using PDI.


Assuntos
Fotoquimioterapia , Fármacos Fotossensibilizantes , Candida albicans , Ácidos Carboxílicos , Clorofila A , Escherichia coli , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Staphylococcus aureus/fisiologia
9.
Photochem Photobiol Sci ; 21(10): 1807-1818, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35816272

RESUMO

The fast-emerging and multidrug-resistant Candida auris is the first fungal pathogen to be considered a threat to global public health. Thus, there is a high unmet medical need to develop new therapeutic strategies to control this species. Antimicrobial photodynamic therapy (APDT) is a promising alternative that simultaneously targets and damages numerous microbial biomolecules. Here, we investigated the in vitro and in vivo effects of APDT with four phenothiazinium photosensitizers: (i) methylene blue (MB), (ii) toluidine blue (TBO), and two MB derivatives, (iii) new methylene blue (NMBN) and (iv) the pentacyclic derivative S137, against C. auris. To measure the in vitro efficacy of each PS, minimal inhibitory concentrations (MICs) and survival fraction were determined. Also, the efficiency of APDT was evaluated in vivo with the Galleria mellonella insect model for infection and treatment. Although the C. auris strain used in our study was shown to be resistant to the most-commonly used clinical antifungals, it could not withstand the damages imposed by APDT with any of the four photosensitizers. However, for the in vivo model, only APDT performed with S137 allowed survival of infected G. mellonella larvae. Our results show that structural and chemical properties of the photosensitizers play a major role on the outcomes of in vivo APDT and underscore the need to synthesize and develop novel photosensitizing molecules against multidrug-resistant microorganisms.


Assuntos
Anti-Infecciosos , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Azul de Metileno/farmacologia , Candida auris , Antifúngicos/farmacologia , Cloreto de Tolônio , Fotoquimioterapia/métodos , Anti-Infecciosos/farmacologia
10.
Pharmaceutics ; 14(7)2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35890401

RESUMO

Nanotechnology-based approaches for targeting the delivery and controlled release of metal-based therapeutic agents have revealed significant potential as tools for enhancing the therapeutic effect of metal-based agents and minimizing their systemic toxicities. In this context, a series of polymer-based nanosized systems designed to physically load or covalently conjugate metal-based therapeutic agents have been remarkably improving their bioavailability and anticancer efficacy. Initially, the polymeric nanocarriers were applied for platinum-based chemotherapeutic agents resulting in some nanoformulations currently in clinical tests and even in medical applications. At present, these nanoassemblies have been slowly expanding for nonplatinum-containing metal-based chemotherapeutic agents. Interestingly, for metal-based photosensitizers (PS) applied in photodynamic therapy (PDT), especially for cancer treatment, strategies employing polymeric nanocarriers have been investigated for almost 30 years. In this review, we address the polymeric nanocarrier-assisted metal-based therapeutics agent delivery systems with a specific focus on non-platinum systems; we explore some biological and physicochemical aspects of the polymer-metallodrug assembly. Finally, we summarize some recent advances in polymeric nanosystems coupled with metal-based compounds that present potential for successful clinical applications as chemotherapeutic or photosensitizing agents. We hope this review can provide a fertile ground for the innovative design of polymeric nanosystems for targeting the delivery and controlled release of metal-containing therapeutic agents.

11.
Biotech Histochem ; 97(7): 473-479, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35852233

RESUMO

The study of labeling selectivity and mechanisms of fluorescent organelle probes in living cells is of continuing interest in biomedical sciences. The tetracationic phthalocyanine-like ZnTM2,3PyPz photosensitizing dye induces a selective violet fluorescence in mitochondria of living HeLa cells under UV excitation that is due to co-localization of the red signal of the dye with NAD(P)H blue autofluorescence. Both red and blue signals co-localize with the green emission of the mitochondria probe, rhodamine 123. Microscopic observation of mitochondria was improved using image processing and analysis methods. High dye concentration and prolonged incubation time were required to achieve optimal mitochondrial labeling. ZnTM2,3PyPz is a highly cationic, hydrophilic dye, which makes ready entry into living cells unlikely. Redox color changes in solutions of the dye indicate that colorless products are formed by reduction. Spectroscopic studies of dye solutions showed that cycles of alkaline titration from pH 7 to 8.5 followed by acidification to pH 7 first lower, then restore the 640 nm absorption peak by approximately 90%, which can be explained by formation of pseudobases. Both reduction and pseudobase formation result in formation of less highly charged and more lipophilic (cell permeant) derivatives in equilibrium with the parent dye. Some of these are predicted to be lipophilic and therefore membrane-permeant; consequently, low concentrations of such species could be responsible for slow uptake and accumulation in mitochondria of living cells. We discuss the wider implications of such phenomena for uptake of hydrophilic fluorescent probes into living cells.


Assuntos
Mitocôndrias , Fármacos Fotossensibilizantes , Corantes Fluorescentes/química , Células HeLa , Humanos , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Compostos Organometálicos , Oxirredução , Fármacos Fotossensibilizantes/metabolismo
12.
Proc Natl Acad Sci U S A ; 119(25): e2123564119, 2022 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-35696565

RESUMO

In the context of the rapid increase of antibiotic-resistant infections, in particular of pneumonia, antimicrobial photodynamic therapy (aPDT), the microbiological application of photodynamic therapy (PDT), comes in as a promising treatment alternative since the induced damage and resultant death are not dependent on a specific biomolecule or cellular pathway. The applicability of aPDT using the photosensitizer indocyanine green with infrared light has been successfully demonstrated for different bacterial agents in vitro, and the combination of pulmonary delivery using nebulization and external light activation has been shown to be feasible. However, there has been little progress in obtaining sufficient in vivo efficacy results. This study reports the lung surfactant as a significant suppressor of aPDT in the lungs. In vitro, the clinical surfactant Survanta® reduced the aPDT effect of indocyanine green, Photodithazine®, bacteriochlorin-trizma, and protoporphyrin IX against Streptococcus pneumoniae. The absorbance and fluorescence spectra, as well as the photobleaching profile, suggested that the decrease in efficacy is not a result of singlet oxygen quenching, while a molecular dynamics simulation showed an affinity for the polar head groups of the surfactant phospholipids that likely impacts uptake of the photosensitizers by the bacteria. Methylene blue is the exception, likely because its high water solubility confers a higher mobility when interacting with the surfactant layer. We propose that the interaction between lung surfactant and photosensitizer must be taken into account when developing pulmonary aPDT protocols.


Assuntos
Antibacterianos , Bactérias , Fotoquimioterapia , Fármacos Fotossensibilizantes , Tensoativos , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Verde de Indocianina/farmacologia , Pulmão/microbiologia , Simulação de Dinâmica Molecular , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Tensoativos/metabolismo
13.
Lasers Med Sci ; 37(8): 3183-3191, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35723829

RESUMO

This study aims to develop and characterize NCL loaded with ZnF16Pc (Pc) for application in antimicrobial photodynamic therapy. For the development of the NLC, the fusion-emulsification technique followed by sonication was applied. NLC and Pc-NLC were characterized in terms of mean diameter (Dm.n), polydispersity index (PdI), zeta potential (ZP), encapsulation efficiency (%EE), transmission electron microscopy (TEM), differential scanning (DSC), photobleaching and singlet oxygen generation in cellular systems (SOSG), and in vitro release assays performed by the beaker method, using dialysis membranes. Cell viability was performed by colony forming units (CFU/mL). The mean size of NLC and Pc-NLC was 158 nm ± 1.49 to 161.80 nm and showed PdI < 0.3 and ZP between -17.8 and -19.9, and stable during storage time (90 days). The TEM presented spherical particles, the Pc-NLC promoted the encapsulation of 75.57% ± 0.58. DSC analysis confirmed that there was no incompatibility between Pc and NLC. The analysis of the photodegradation profile proved to be photostable after encapsulation and this corroborates the data obtained by SOSG. In vitro release showed controlled and prolonged release. PDT Pc-NLC exhibited greater antifungal effect against C. albicans (3 log10 reduction) than Pc-NLC without light (1 log10 reduction). NLC can be an alternative to the application of Pc and improve the effect during PDT treatment.


Assuntos
Candida albicans , Nanoestruturas , Antifúngicos/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Indóis , Lipídeos/química , Nanoestruturas/química , Compostos Organometálicos , Tamanho da Partícula , Oxigênio Singlete
14.
J Photochem Photobiol B ; 231: 112459, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35512577

RESUMO

The emergence of opportunistic pathogens and the selection of resistant strains have created a grim scenario for conventional antimicrobials. Consequently, there is an ongoing search for alternative techniques to control these microorganisms. One such technique is antimicrobial photodynamic therapy (aPDT), which combines photosensitizers, light, and molecular oxygen to produce reactive oxygen species and kill the target pathogen. Here, the in vitro susceptibilities of three fungal pathogens, namely Candida albicans, Aspergillus nidulans, and Colletotrichum abscissum to aPDT with zinc(II) phthalocyanine (ZnPc) derivative complexes were investigated. Three ZnPc bearing thiopyridinium substituents were synthesized and characterized by several spectroscopic techniques. The Q-band showed sensitivity to the substituent with high absorptivity coefficient in the 680-720 nm region. Derivatization and position of the rings with thiopyridinium units led to high antifungal efficiency of the cationic phthalocyanines, which could be correlated with singlet oxygen quantum yield, subcellular localization, and cellular uptake. The minimum inhibitory concentrations (MIC) of the investigated ZnPc-R complexes against the studied microorganisms were 2.5 µM (C. albicans) and 5 µM (A. nidulans and C. abscissum). One ZnPc derivative achieved complete photokilling of C. albicans and, furthermore, yielded low MIC values when used against the tolerant plant-pathogen C. abscissum. Our results show that chemical modification is an important step in producing better photosensitizers for aPDT against fungal pathogens.


Assuntos
Anti-Infecciosos , Fotoquimioterapia , Antibacterianos , Anti-Infecciosos/farmacologia , Candida albicans , Isoindóis , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia
15.
Methods Mol Biol ; 2451: 261-283, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35505023

RESUMO

The development of improved photosensitizers is a key aspect in the establishment of photodynamic therapy (PDT) as a reliable treatment modality. In this chapter, we discuss how molecular design can lead to photosensitizers with higher selectivity and better efficiency, with focus on the importance of specific intracellular targeting in determining the cell death mechanism and, consequently, the PDT outcome.


Assuntos
Fotoquimioterapia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico
16.
Photodiagnosis Photodyn Ther ; 38: 102788, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35235837

RESUMO

BACKGROUND: A plant extract (EB) incorporated into glass ionomer cement (GIG) could be a potential photosensitizer for Antimicrobial PDT (aPDT) against caries-microorganisms, replacing methylene blue (MB), due to the presence of chlorophyll. GIC + EB + aPDT could be an therapeutic alternative to dentin decontamination and sealing, allowing reduction of operative time. OBJECTIVE: Evaluate Dioscorea altissima (EB) incorporated into GIC as a photosensitizer for aPDT against Streptococcus mutans. METHODS: Groups (n = 24; ntotal = 192): G1-GIC; G2-GIC + LASER; G3-GIC/EB; G4-GIC/EB + LASER; G5-GIC+MB; G6-GIC + aPDT; G7-GIC/EB + MB; and G8 - GIC/EB+aPDT. In aPDT groups, MB was the photosensitizer. In LASER groups, MB was not used. The irradiation protocol was 660 nm/100 mW/5 J/150 J/cm²/50 s, with a 5-min pre-irradiation time for the MB groups. Antibacterial assays were carried out in 24-well microplates. The wells were completed with one milliliter of a S. mutans in BHI at 1.3 × 108 CFU/mL suspension. After incubation, PDT or laser was performed. After MTT bacteria viability test, the data were submitted to the Kolgomorov-Smirnoff normality test, followed by one-way ANOVA and Tukey's posterior test, α < 0.05. RESULTS: Group G6 showed significant inhibition (p < 0.001), followed by groups G4, G5, G7, and G8, which did not show significant differences among them (p > 0.05). Groups G2 and G3 also showed similar results (p > 0.05) and were the least active compared to the others. CONCLUSIONS: EB potentiated the antimicrobial action of GIC against S. mutans and laser irradiation over GIC/EB presented better antimicrobials results. The results indicate that EB could be a potential photosensitizer for aPDT.


Assuntos
Anti-Infecciosos , Fotoquimioterapia , Antibacterianos/farmacologia , Anti-Infecciosos/uso terapêutico , Biofilmes , Cimentos de Ionômeros de Vidro , Azul de Metileno/farmacologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Extratos Vegetais/farmacologia , Streptococcus mutans
17.
Spectrochim Acta A Mol Biomol Spectrosc ; 270: 120817, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35030417

RESUMO

In this article, Density Functional Theory based calculations, including dispersion corrections, PBE0(D3BJ)/Def2-TZVP(-f), were performed to elucidate the photophysics of the [Ru(bpy)2(HAT)]2+ complex in water. In addition, the thermodynamics of the charge and electron transfer excited state reactions of this complex with oxygen, nitric oxide and Guanosine-5'-monophosphate nucleotide (GMP) were investigated. The first singlet excite state, S1, strongly couples with the second and third triplet excited states (T2 and T3) giving rise to a high intersystem crossing rate of 6.26 × 1011 s-1 which is ∼106 greater than the fluorescence rate decay. The thermodynamics of the excited reactions revealed that all electron transfer reactions investigated are highly favorable, due mainly to the high stability of the triply charged radical cation 2PS•3+ species formed after the electron has been transferred. Excited state electron transfer from the GMP nucleotide to the complex is also highly favorable (ΔGsol = -92.6 kcal/mol), showing that this complex can be involved in the photooxidation of DNA, in line with experimental findings. Therefore, the calculations allow to conclude that the [Ru(bpy)2(HAT)]2+ complex can act in Photodynamic therapy through both mechanisms type I and II, through electron transfer from and to the complex and triplet-triplet energy transfer, generating ROS, RNOS and through DNA photooxidation. In addition, the work also opens a perspective of using this complex for the in-situ generation of the singlet nitroxyl (1NO-) species, which can have important applications for the generation of HNO and may have, therefore, important impact for physiological studies involving HNO.


Assuntos
Compostos Organometálicos , Rutênio , 2,2'-Dipiridil , Compostos Aza , Crisenos , Elétrons
18.
Chemistry ; 28(5): e202103884, 2022 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-34878698

RESUMO

A novel BOPHY-fullerene C60 dyad (BP-C60 ) was designed as a heavy-atom-free photosensitizer (PS) with potential uses in photodynamic treatment and reactive oxygen species (ROS)-mediated applications. BP-C60 consists of a BOPHY fluorophore covalently attached to a C60 moiety through a pyrrolidine ring. The BOPHY core works as a visible-light-harvesting antenna, while the fullerene C60 subunit elicits the photodynamic action. This fluorophore-fullerene cycloadduct, obtained by a straightforward synthetic route, was fully characterized and compared with its individual counterparts. The restricted rotation around the single bond connecting the BOPHY and pyrrolidine moieties led to the formation of two atropisomers. Spectroscopic, electrochemical, and computational studies disclose an efficient photoinduced energy/electron transfer process from BOPHY to fullerene C60 . Photodynamic studies indicate that BP-C60 produces ROS by both photomechanisms (type I and type II). Moreover, the dyad exhibits higher ROS production efficiency than its individual constitutional components. Preliminary screening of photodynamic inactivation on bacteria models (Staphylococcus aureus and Escherichia coli) demonstrated the ability of this dyad to be used as a heavy-atom-free PS. To the best of our knowledge, this is the first time that not only a BOPHY-fullerene C60 dyad is reported, but also that a BOPHY derivative is applied to photoinactivate microorganisms. This study lays the foundations for the development of new BOPHY-based PSs with plausible applications in the medical field.


Assuntos
Anti-Infecciosos , Fulerenos , Fotoquimioterapia , Anti-Infecciosos/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Staphylococcus aureus
20.
J Photochem Photobiol B ; 226: 112365, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34823208

RESUMO

The widespread use of conventional chemical antifungal agents has led to worldwide concern regarding the selection of resistant isolates. In this scenario, antimicrobial photodynamic treatment (APDT) has emerged as a promising alternative to overcome this issue. The technique is based on the use of a photosensitizer (PS) and light in the presence of molecular oxygen. Under these conditions, the PS generates reactive oxygen species which damage the biomolecules of the target organism leading to cell death. The great potential of APDT against plant-pathogenic fungi has already been reported both in vitro and in planta, indicating this control measure has the potential to be widely used in crop plants. However, there is a lack of studies on environmental risk with ecotoxicological assessment of PSs used in APDT. Therefore, this study aimed to evaluate the environmental toxicity of four phenothiazinium PSs: i) methylene blue (MB), ii) new methylene blue N (NMBN), iii) toluidine blue O (TBO), and iv) dimethylmethylene blue (DMMB) and also of the commercial antifungal NATIVO®, a mixture of trifloxystrobin and tebuconazole. The experiments were performed with Daphnia similis neonates and zebrafish embryos. Our results showed that the PSs tested had different levels of toxicity, with MB being the less toxic and DMMB being the most. Nonetheless, the environmental toxicity of these PSs were lower when compared to that of NATIVO®. Furthermore, estimates of bioconcentration and of biotransformation half-life indicated that the PSs are environmentally safer than NATIVO®. Taken together, our results show that the toxicity associated with phenothiazinium PSs would not constitute an impediment to their use in APDT. Therefore, APDT is a promising approach to control plant-pathogenic fungi with reduced risk for selecting resistant isolates and lower environmental impacts when compared to commonly used antifungal agents.


Assuntos
Triazóis
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