Navegação por Autores IPEN "CABRAL, FERNANDA V."

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  • IPEN-DOC 28354

    CABRAL, FERNANDA V. ; LIAN, CHENG; PERSHEYEV, SAYDULLA; SMITH, TERRY K.; RIBEIRO, MARTHA S. ; SAMUEL, IFOR D.W.. Organic light-emitting diodes as an innovative approach for treating cutaneous leishmaniasis. Advanced Materials Technologies, v. 6, n. 11, p. 1-9, 2021. DOI: 10.1002/admt.202100395

    Abstract: Antimicrobial photodynamic therapy (APDT) has been studied as a noninvasive therapy for treating cutaneous leishmaniasis to overcome challenges with current treatment, such as toxicity, resistance, and need for in-patient hospital treatment. Organic light-emitting diodes (OLEDs) have emerged as an attractive technology that can provide wearable light-emitting materials that are conformable to human skin. This makes OLEDs ideal candidates for APDT by light-bandages for ambulatory care. In this work, suitable OLEDs are successfully developed to match the absorbance of three photosensitizers: methylene blue, new methylene blue, and 1,9-dimethyl-methylene blue to inactivate two Leishmania species in vitro: Leishmania major and Leishmania amazonensis. Parasites are treated either by LED (20 mW cm−2) or OLED (6.5 mW cm−2) at increasing photosensitizer concentrations at a radiant exposure of 50 J cm−2. 1,9-Dimethyl-methylene blue is the most potent photosensitizer, killing both strains at nanomolar concentrations. The effect of different intensities from the OLEDs (0.7, 1.5, and 6.5 mW cm−2) are also explored and it is shown that effective killing of Leishmania occurs even at a very low intensity. These findings demonstrate the great potential of OLEDs as a new approach for ambulatory treatment of cutaneous leishmaniasis by APDT.

    Palavras-Chave: antibiotics; antimicrobial agents; light emitting diodes; organic compounds; parasites; photosensitivity

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  • IPEN-DOC 29355

    CABRAL, FERNANDA V. ; LIAN, CHENG; PERSHEYEV, SAYDULLA; SAMUEL, IFOR D.W.; RIBEIRO, MARTHA S. . Organic light-emitting diodes as wearable light sources for antiparasitic photodynamic therapy. In: LATIN AMERICA OPTICS AND PHOTONICS CONFERENCE, August 7-11, 2022, Recife, PE. Proceedings... Washington, DC, USA: Optica Publishing Group, 2022. DOI: 10.1364/LAOP.2022.Tu4A.39

    Abstract: Herein, we used a photosensitizing agent and red organic light-emitting diodes (OLEDs) against two strains of Leishmania amazonensis amastigotes, including a drug-resistant line. OLEDs are promising wearable light sources for photodynamic therapy of cutaneous leishmaniasis.

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  • IPEN-DOC 30132

    SILVA, ABDENEGO R. ; CABRAL, FERNANDA V. ; SILVA, CAMILA R. ; SILVA, DANIELA F.T. ; FREITAS, ANDERSON Z. ; FONTES, ADRIANA; RIBEIRO, MARTHA S. . Photodynamic inactivation against the critical priority pathogen Candida auris. In: ANNUAL MEETING OF THE BRAZILIAN BIOPHYSICAL SOCIETY, 47th, October 19-22, 2023, Campinas, SP. Abstract... Campinas, SP: Galoá, 2023.

    Abstract: Fungal pathogens and their associated infections present a growing challenge to global public health. Among these pathogens, Candida auris has emerged as a highly hazardous hospital-acquired microorganism, included in the critical priority group by the World Health Organization. Methylene Blue (MB) is a widely acknowledged photosensitizer utilized in antifungal photodynamic inactivation (PDI) and holds significant clinical applications. The MB methylation results in the formation of a more lipophilic compound, the 1,9-dimethyl MB (DMMB), which can have an enhanced interaction with cell membranes. Nevertheless, PDI mediated by DMMB to combat fungi remains little explored. In this study, we assessed the impact and underlying mechanisms of PDI using MB (MB-PDI) or DMMB (DMMB-PDI) combined with a red LED against C. auris. PDI was conducted on the CBS 10913 strain of C. auris, utilizing different concentrations of MB (0 – 100 μM) or DMMB (0 – 3 μM) at light doses of 10 or 30 J/cm². To evaluate the PDI efficacy, we measured colony-forming units and monitored reactive oxygen species (ROS) production. Additionally, we assessed lipid peroxidation (LPO) and mitochondrial membrane potential (ΔΨm) to gain insights into the differences between MB and DMMB. Our findings revealed that DMMB-PDI successfully eradicated C. auris yeasts at 3 μM concentration, irrespective of the light dose, whereas MB (100 μM) only exhibited cell eradication at the highest light dose. ROS formation was more pronounced for DMMB than MB at 10 J/cm2. At 30 J/cm2, MB and DMMB produced similar ROS levels. In sublethal conditions, DMMB-PDI induced significantly higher LPO, and ΔΨm levels compared to MB-PDI. Furthermore, DMMB-PDI effectively inhibited biofilm formation and disrupted mature biofilms, with no observed toxicity in fibroblast cells. In conclusion, our study demonstrates the potential of DMMB-PDI as a promising weapon to combat the global priority pathogen C. auris. The enhanced PDI efficacy and biofilm eradication capacity of DMMB make it a valuable candidate for further exploration in the fight against this hazardous pathogen. As the incidence of drug-resistant fungal infections continues to rise, the development of innovative and effective therapeutic strategies like DMMB-PDI is crucial in safeguarding public health worldwide.

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  • IPEN-DOC 29710

    CABRAL, FERNANDA V. ; YOSHIMURA, TANIA M. ; SILVA, DANIELA de F.T. da ; CORTEZ, MAURO; RIBEIRO, MARTHA S. . Photodynamic therapy mediated by a red LED and methylene blue inactivates resistant leishmania amazonensis. Journal of the Optical Society of America A, v. 40, n. 5, p. 996-1005, 2023. DOI: 10.1364/JOSAA.482314

    Abstract: Cutaneous leishmaniasis is a neglected parasitic disease that leads to destructive lesions. The emergence of drug resistance has been a global concern over the past years. Photodynamic therapy (PDT) mediated by a red LED and methylene blue (MB) involves the overproduction of oxidative stress, which oxidizes several cellular biomolecules and prevents the selection of resistant strains. Herein, we investigated the potential of PDT mediated by MB against wild-type and miltefosine-resistant strains of Leishmania amazonensis. As a result, both strains were susceptible to PDT, thus encouraging us to seek the best conditions to overcome the drug resistance problem in cutaneous leishmaniasis.

    Palavras-Chave: protozoa; parasitic diseases; skin diseases; photodynamic therapy; methylene blue; light emitting diodes

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  • IPEN-DOC 25031

    DIMMER, JESICA; CABRAL, FERNANDA V. ; SABINO, CAETANO P. ; NUNEZ MONTOYA, SUSANA C.; CABRERA, JOSE L.; RIBEIRO, MARTHA S. . Photoinactivation of Leishmania amazonesis by natural anthraquinones. In: INTERNATIONAL PHOTODYNAMIC ASSOCIATION WORLD CONGRESS, 16th, June 08-13, 2017, Coimbra, Portugal. Abstract... 2017. p. 195-195.

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  • IPEN-DOC 29924

    CABRAL, FERNANDA V. ; SANTANA, BIANCA de M.; LANGE, CAMILA N.; BATISTA, BRUNO L.; SEABRA, AMEDEA B.; RIBEIRO, MARTHA S . Pluronic F-127 hydrogels containing copper oxide nanoparticles and a nitric oxide donor to treat skin cancer. Pharmaceutics, v. 15, n. 1971, p. 1-19, 2023. DOI: 10.3390/ pharmaceutics15071971

    Abstract: Melanoma is a serious and aggressive type of skin cancer with growing incidence, and it is the leading cause of death among those affected by this disease. Although surgical resection has been employed as a first-line treatment for the early stages of the tumor, noninvasive topical treatments might represent an alternative option. However, they can be irritating to the skin and result in undesirable side effects. In this context, the potential of topical polymeric hydrogels has been investigated for biomedical applications to overcome current limitations. Due to their biocompatible properties, hydrogels have been considered ideal candidates to improve local therapy and promote wound repair. Moreover, drug combinations incorporated into the polymeric-based matrix have emerged as a promising approach to improve the efficacy of cancer therapy, making them suitable vehicles for drug delivery. In this work, we demonstrate the synthesis and characterization of Pluronic F-127 hydrogels (PL) containing the nitric oxide donor S-nitrosoglutathione (GSNO) and copper oxide nanoparticles (CuO NPs) against melanoma cells. Individually applied NO donor or metallic oxide nanoparticles have been widely explored against various types of cancer with encouraging results. This is the first report to assess the potential and possible underlying mechanisms of action of PL containing both NO donor and CuO NPs toward cancer cells. We found that PL + GSNO + CuO NPs significantly reduced cell viability and greatly increased the levels of reactive oxygen species. In addition, this novel platform had a huge impact on different organelles, thus triggering cell death by inducing nuclear changes, a loss of mitochondrial membrane potential, and lipid peroxidation. Thus, GSNO and CuO NPs incorporated into PL hydrogels might find important applications in the treatment of skin cancer.

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  • IPEN-DOC 26678

    CABRAL, FERNANDA V. ; SABINO, CAETANO P.; DIMMER, JESICA A.; SAUTER, ISMAEL P. ; CORTEZ, MAURO J.; RIBEIRO, MARTHA S. . Preclinical investigation of methylene blue-mediated antimicrobial photodynamic therapy on Leishmania parasites using real-time bioluminescence. Photochemistry and Photobiology, v. 96, n. 3, p. 604-610, 2020. DOI: 10.1111/php.13188

    Abstract: Cutaneous leishmaniasis (CL) is a neglected disease that promotes destructive lesions. Difficulties in treatment are related to accessibility of drugs, resistance and toxicity. Antimicrobial photodynamic therapy (APDT) has been emerging as a promising treatment for CL. In this work, we evaluated methylene blue (MB)-mediated APDT (MB-APDT) on Leishmania amazonensis in vitro and in vivo by bioluminescence technique. In vitro, MB-APDT was performed using a red LED (k = 660 11 nm, 100 mW cm 2) and MB (100 μM) at different light doses. In vivo, mice were infected and 4 weeks later, randomly divided into three groups: control, APDT 1 (single session) and APDT 2 (two sessions of MB-APDT). MB was used at 100 μM and energy dose was established at 150 J cm 2. Parasite burden, lesion size and pain were evaluated weekly for 4 weeks. In vitro, lethal dose for 90% parasite inactivation was achieved at 48.8 J cm 2. In vivo, although APDT 1 and APDT 2 groups have showed similar parasite burden after 4 weeks, two sessions were clinically better, especially considering the inflammatory process associated to CL. Our findings reinforce MB-APDT as a costeffective treatment to combat CL.

    Palavras-Chave: antimicrobial agents; therapy; photosensitivity; methylene blue; parasites; bioluminescence; photochemistry; in vivo; in vitro; mice

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  • IPEN-DOC 29840

    CABRAL, FERNANDA V. ; SOUZA, TIAGO H. dos S.; SALLERA, FABIO P.; FONTES, ADRIANA; RIBEIRO, MARTHA S. . Strengthening collaborations at the Biology‑Physics interface: trends in antimicrobial photodynamic therapy. Biophysical Reviews, v. 15, n. 4, p. 685-697, 2023. DOI: 10.1007/s12551-023-01066-5

    Abstract: The unbridled use of antimicrobial drugs over the last decades contributed to the global dissemination of drug-resistant pathogens and increasing rates of life-threatening infections for which limited therapeutic options are available. Currently, the search for safe, fast, and efective therapeutic strategies to combat infectious diseases is a worldwide demand. Antimicrobial photodynamic therapy (APDT) rises as a promising therapeutic approach against a wide range of pathogenic microorganisms. APDT combines light, a photosensitizing drug (PS), and oxygen to kill microorganisms by oxidative stress. Since the APDT feld involves branches of biology and physics, the strengthening of interdisciplinary collaborations under the aegis of biophysics is welcome. Given this scenario, Brazil is one of the global leaders in the production of APDT science. In this review, we provide detailed reports of APDT studies published by the Laboratory of Optical Therapy (IPEN-CNEN), Group of Biomedical Nanotechnology (UFPE), and collaborators over the last 10 years. We present an integrated perspective of APDT from basic research to clinical practice and highlight its promising use, encouraging its adoption as an efective and safe technology to tackle important pathogens. We cover the use of methylene blue (MB) or Zn(II) porphyrins as PSs to kill bacteria, fungi, parasites, and pathogenic algae in laboratory assays. We describe the impact of MB-APDT in Dentistry and Veterinary Medicine to treat diferent infectious diseases. We also point out future directions combining APDT and nanotechnology. We hope this review motivates further APDT studies providing intuitive, vivid, and insightful information for the readers.

    Palavras-Chave: antimicrobial agents; methylene blue; inactivation; photodynamic therapy; photosensitivity; porphyrins; zinc

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  • IPEN-DOC 28315

    SELLERA, FABIO P.; SABINO, CAETANO P.; CABRAL, FERNANDA V. ; RIBEIRO, MARTHA S. . A systematic scoping review of ultraviolet C (UVC) light systems for SARS-CoV-2 inactivation. Journal of Photochemistry and Photobiology, v. 8, p. 1-6, 2021. DOI: 10.1016/j.jpap.2021.100068

    Abstract: A significant amount of epidemiological evidence has underlined that human-to-human transmission due to close contacts is considered the main pathway of transmission, however since the SARS-CoV-2 can also survive in aerosols, water, and surfaces, the development and implementation of effective decontamination strategies are urgently required. In this regard, ultraviolet germicidal irradiation (UVGI) using ultraviolet C (UVC) has been proposed to disinfect different environments and surfaces contaminated by SARS-CoV-2. Herein, we performed a systematic scoping review strictly focused on peer-reviewed studies published in English that reported experimental results of UVC-based technologies against the SARS-CoV-2 virus. Studies were retrieved from PubMed and the Web of Science database. After our criterious screening, we identified 13 eligible articles that used UVC-based systems to inactivate SARS-CoV-2. We noticed the use of different UVC wavelengths, technologies, and light doses. The initial viral titer was also heterogeneous among studies. Most studies reported virus inactivation in well plates, even though virus persistence on N95 respirators and different surfaces were also evaluated. SARS-CoV-2 inactivation reached from 90% to 100% depending on experimental conditions. We concluded that there is sufficient evidence to support the use of UVC-based technologies against SARS-CoV-2. However, appropriate implementation is required to guarantee the efficacy and safety of UVC strategies to control the COVID-19 pandemic.

    Palavras-Chave: coronaviruses; inactivation; germicides; ultraviolet radiation; photoreactivation

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  • IPEN-DOC 28857

    COLLINA, GABRIELA A. da; CABRAL, FERNANDA V. ; MONTEIRO, CAROLINA M.; MACHADO, GABRIELA B.; GONCALVES, JOSE M.L.A.; FREIRE, FERNANDA; PRATES, RENATO A.; RIBEIRO, MARTHA S. ; PAVANI, CHRISTIANE. The importance of combining methods to assess Candida albicans biofilms following photodynamic inactivation. Photodiagnosis and Photodynamic Therapy, v. 38, p. 1-6, 2022. DOI: 10.1016/j.pdpdt.2022.102769

    Abstract: Background: Methylene blue (MB)-mediated photodynamic inactivation (PDI) has shown good results in killing Candida spp. Although MB solutions are commonly used, new formulations have been designed to improve PDI. However, chemical substances in the formulation may interfere with the PDI outcome. In this sense, different methodologies should be used to evaluate PDI in vitro. Herein, we report different methodologies to evaluate the effects of PDI with an oral formulation (OF) containing 0.005% MB on Candida albicans biofilm. Methods: Biofilms were treated using the MB-OF, with 5 min pre-irradiation time and exposure to a 640 nm LED device (4.7 J/cm2). PDI was evaluated by the XTT reduction test, counting the colony forming units (CFU), a filamentation assay, crystal violet (CV) staining, and scanning electronic microscopy (SEM). Results: PDI was able to reduce around 1.5 log10 CFU/mL, even though no significant differences were noted in metabolic activity in comparison to the control immediately after PDI. A significant decrease in yeast to hyphae transition was observed after PDI, while the biofilm exhibited flattened cells and a reduced number of yeasts in SEM. The CV assay showed increased biomass. Conclusion: MB-OF-mediated PDI was effective in C. albicans biofilms, as it significantly reduced the CFU/mL and the virulence of surviving cells. The CV data were inconclusive, since the OF components interacted with the CV, making the data useless. Taken together, our data suggest that the association of different methods allows complementary responses to assess how PDI mediated by a formulation impacts biofilms.

    Palavras-Chave: antimicrobial agents; methylene blue; chemotherapy; photodynamic therapy

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  • IPEN-DOC 28366

    CABRAL, FERNANDA V. ; SOUZA, TIAGO H. dos S.; SELLERA, FABIO P.; FONTES, ADRIANA; RIBEIRO, MARTHA S. . Towards effective cutaneous leishmaniasis treatment with light-based technologies. A systematic review and meta-analysis of preclinical studies. Journal of Photochemistry and Photobiology B: Biology, v. 221, p. 1-8, 2021. DOI: 10.1016/j.jphotobiol.2021.112236

    Abstract: Cutaneous leishmaniasis (CL) is a neglected disease that represents a serious global public health concern. We performed a systematic review with meta-analysis targeting the use of light-based therapies on CL in preclinical studies since they are essential to identify the benefits, challenges, and limitations of proposing new technologies to fight CL. We searched Pubmed and Web of Science to include original preclinical researches in English that used light-based technologies to fight CL. Inclusion criteria encompassed any animal model for CL induction, an untreated infected group as the comparator, reliable and consistent methodology to develop and treat CL, focus on an antimicrobial therapeutic approach, and data for lesion size and/or parasite load in the infection site. We identified eight eligible articles, and all of them used photodynamic therapy (PDT). For the meta-analysis, three studies were included regarding the parasite load in the infection site and four comprised the lesion size. No overall statistically significant differences were observed between untreated control and PDT groups for parasite load. Differently, PDT significantly reduced the lesion size regardless of the protocol used to treat CL (in mm, SMD: -1.90; 95% CI: −3.74 to −0.07, p = 0.04). This finding is particularly encouraging since CL promotes disfiguring lesions that profoundly affect the quality of life of patients. We conclude that PDT is a new promising technology able to be topically used against CL if applied in more than one session, making it a promising ally for the management of CL.

    Palavras-Chave: protozoa; antimicrobial agents; therapy; photosensitivity

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  • IPEN-DOC 28484

    CABRAL, FERNANDA V. . Towards new therapeutic strategies for cutaneous leishmaniasis / Buscando novas estratégias terapêuticas para o tratamento de leishmaniose cutânea . 2021. Tese (Doutorado em Tecnologia Nuclear) - Instituto de Pesquisas Energéticas e Nucleares - IPEN-CNEN/SP, São Paulo. 123 p. Orientador: Martha Simões Ribeiro. DOI: 10.11606/T.85.2021.tde-18112021-095721

    Abstract: Cutaneous leishmaniasis (CL) is a zoonotic disease developed by protozoa parasites of genus Leishmania. It promotes destructive and ulcerated lesions with limited treatment options. There is an urgent need for the development of topical, cost-effective and efficacious treatments with minimized side effects to treat affected patients. The parasite-host interaction is of great importance since Leishmania parasites survive and replicate within host macrophages. As phagocytic cells, the activated macrophages produce reactive oxygen species (ROS) and nitric oxide (NO), which are toxic to pathogens, hence preventing parasites proliferation. However, Leishmania parasites can evade the host immune response and subvert antimicrobial macrophage defenses, thereby surviving within these cells even in harsh conditions. Indeed, the role played by ROS and NO in the control of CL has been under debate over the past years, emerging as potential alternatives to tackle this important neglected disease. In this regard, we aimed to evaluate the role of both NO and ROS towards antileishmanial activity using two different therapeutic strategies: (1) nitric oxide-releasing chitosan nanoparticles (NONPs) and (2) antimicrobial photodynamic therapy (PDT). For this, we focused on development and investigation of the potential of NONPs in vitro and in vivo against Leishmania amazonensis, one of the causative agents of CL. To assess the role of ROS, photodynamic therapy was investigated against different Leishmania species. Firstly, we evaluated the potential of organic light-emitting diodes (OLEDs) as a novel light source to inactivate in vitro promastigotes of L. major and L. amazonensis, using three phenothiazine dyes: Methylene blue, new methylene blue and 1,9-dimethyl methylene blue (DMMB). Then, we addressed the underlying mechanisms of DMMB-PDT upon promastigotes of L. amazonensis wild-type (WT) and miltefosineresistant (MFR) strains. DMMB-PDT effectiveness was also evaluated against intracellular amastigotes of WT and MFR together with cytotoxicity assay on mammalian cells. Our findings demonstrate that either NONPs or PDT are promising strategies to target CL and should be further explored for future preclinical and clinical trials.

    Palavras-Chave: parasites; trypanosomes; skin diseases; chemical oxygen demand; nitric oxide; spectroscopy; light emitting diodes

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  • IPEN-DOC 27319

    RIBEIRO, MARTHA S. ; YOSHIMURA, TANIA M. ; CABRAL, FERNANDA V. ; SILVA, CAMILA R. . Anais do I Fórum on-line de Tecnologias da Luz na Saúde. São Paulo, SP: Universidade Brasil, 2020. 89 p.

    Palavras-Chave: visible radiation; light sources; medicine; dentistry; therapeutic uses; ultraviolet radiation; therapy

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A elaboração do projeto do RI do IPEN foi iniciado em novembro de 2013, colocado em operação interna em julho de 2014 e disponibilizado na Internet em junho de 2015. Utiliza o software livre Dspace, desenvolvido pelo Massachusetts Institute of Technology (MIT). Para descrição dos metadados adota o padrão Dublin Core. É compatível com o Protocolo de Arquivos Abertos (OAI) permitindo interoperabilidade com repositórios de âmbito nacional e internacional.

O gerenciamento do Repositório está a cargo da Biblioteca do IPEN. Constam neste RI, até o presente momento 20.950 itens que tanto podem ser artigos de periódicos ou de eventos nacionais e internacionais, dissertações e teses, livros, capítulo de livros e relatórios técnicos. Para participar do RI-IPEN é necessário que pelo menos um dos autores tenha vínculo acadêmico ou funcional com o Instituto. Nesta primeira etapa de funcionamento do RI, a coleta das publicações é realizada periodicamente pela equipe da Biblioteca do IPEN, extraindo os dados das bases internacionais tais como a Web of Science, Scopus, INIS, SciElo além de verificar o Currículo Lattes. O RI-IPEN apresenta também um aspecto inovador no seu funcionamento. Por meio de metadados específicos ele está vinculado ao sistema de gerenciamento das atividades do Plano Diretor anual do IPEN (SIGEPI). Com o objetivo de fornecer dados numéricos para a elaboração dos indicadores da Produção Cientifica Institucional, disponibiliza uma tabela estatística registrando em tempo real a inserção de novos itens. Foi criado um metadado que contém um número único para cada integrante da comunidade científica do IPEN. Esse metadado se transformou em um filtro que ao ser acionado apresenta todos os trabalhos de um determinado autor independente das variáveis na forma de citação do seu nome.