JORGE GABRIEL DOS SANTOS BATISTA

JORGE GABRIEL DOS SANTOS BATISTA

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Fabrication of green nanomaterials
2023 - THIPE, VELAPHI C.; FREITAS, LUCAS F.; LIMA, CAROLINE S.A.; BATISTA, JORGE G.S.; FERREIRA, ARYEL H.; OLIVEIRA, JUSTINE P.R. de; BALOGH, TATIANA S.; KADLUBOWSKI, SLAWOMIR; LUGAO, ADEMAR B.; KATTI, KATTESH V.
The purpose of this chapter is to discuss the production of biocompatible green nanomaterials for biomedical applications using green nanotechnology. To enhance drug loading and delivery, these nanomaterials are engineered with immunomodulatory ligands such as phytochemicals (Epigallocatechin gallate, Mangiferin, Resveratrol), proteins (albumin and papain), crosslinked hydrogels, and nanogels. The nanomaterials described herein are synthesized via redox potential of electron-dense phytochemicals that reduce metallic precursors to their stable corresponding nanoparticles and via water radiolysis with ionizing radiation as a green approach (due to the absence of any reducing agent) for use as radiosensitizers (albumin and papain nanoparticles) in nuclear medicine – theranostics applications. The phytochemicals facilitate the delivery of nanoparticles through receptor mediated endocytosis, while the proteins such as papain, due to their proteolytic action enhances the permeation of nanoparticles into tumor tissue, and albumin increase the pharmacokinetic efficiency of these nanoparticles. The nanoparticles developed have shown effectiveness against a variety of human cancers while posing no toxicity to normal tissue. Additionally, a pilot human clinical combing Ayurvedic medicine with green nanomedicine is given as a novel approach for treating breast cancer and other related illnesses. Finally, the importance of ecotoxicology for nanomaterials is discussed in order to provide safety data in relevant multiple species (fish, daphnia, algae, rodents, etc.) with paratope/epitope distributions for evaluating tissue cross-reactivity profiles in human tissues and to provide critical information on in vivo toxicity in order to predict the possible adverse effects of nanomaterials on human and environmental health as an effort to establish regulatory limits and ISO standards for nanomaterials.
Aplicação de nanopartículas de ouro preparadas com ácido tânico em células cancerígenas
2022 - SPADREZANO, I.; FREITAS, L.F. de; BATISTA, J.G.; SOUSA, T.d.; LUGAO, A.B.
As nanopartículas de ouro (AuNPs) apresentam propriedades essenciais para diagnóstico e terapia, como facilidade na sua síntese, nas modificações de sua superfície, no controle de monodispersão da solução e do tamanho. A partir de modificação química da superfície, a redução de ouro oriunda de fitoquímicos para a formação de nanopartículas é um método promissor da nanotecnologia verde. O composto responsável pela redução e estabilização, nesse respectivo trabalho, é o ácido tânico (AT) obtido através da hidrólise do tanino, um polifenol sintetizado pelas plantas. O AT possui atividade antioxidante, proporcionada pelas hidroxilas presentes na molécula, neutralizando a atividade de radicais livres gerados no organismo. Uma das principais causas dos cânceres é decorrente da fosforilação anormal dos resíduos de tirosina que faz com que a fosforilação seja mantida, levando a uma ativação permanente dos sinais de transdução. As proteínas tirosinas quinases (PTKs) são um grupo de enzimas responsável por catalisar a fosforilação dos resíduos de tirosina nas proteínas, sendo necessária para a manutenção do estado cancerígeno. O AT possui alta capacidade de inibição das PTKs. A síntese de AuNPs-AT foi estabelecida pelo procedimento de redução química, utilizando uma solução de sal de ouro (NaAuCl4) que foi acrescida em uma solução de AT sob refrigeração. Os diâmetros hidrodinâmicos medidos na amostra não centrifugada, designada como NC, apresentou tamanho 37,88 nm, na amostra centrifugada uma vez, nomeada como S1, 38,85 nm e na amostra centrifugada duas vezes, denominada como S2, 40,50 nm. Foi perceptível o efeito das centrifugações a fim de retirar o excesso de agente estabilizante que não reagiu, foi permitido uma maior agregação das nanopartículas, segregando os variados tamanhos. Os valores do índice de polidispersão (PDI) das AuNPs-AT estão na faixa de 0,245 – 0,262, sendo considerada como de polidispersividade média, supondo que os agregados de nanopartículas estavam com tamanhos uniformes entre si. A citotoxicidade sobre as células MCF-7 (células tumorais) e HUVEC (células não tumorais) foi realizada por meio do método MTT, com a concentração de 25% e 50%. Houve um aumento significativo dos índices de absorbância em concentração 50%, induzido pela amostra AuNPs-AT S2 em células não tumorais, indicando menor citotoxicidade. No caso das células tumorais, induzidas pelas AuNPs-AT NC em concentração de 25% foram capazes de causar morte celular. Os resultados provaram, de forma satisfatória e aprimorada, a formação de AuNPs pelo método de síntese verde com as alterações propostas. O revestimento através do ácido tânico apresentou maior eficiência na inibição e efeito antitumoral, conforme mostrado nos ensaios de citotoxicidade. Nesse estudo, as nanopartículas tinham diâmetro de ? 39,08 nm, o tamanho e o recobrimento não foram consideravelmente tóxicos em aplicações para fins médicos. No geral, as AuNPs-AT foram bem toleradas pelas células.
The role of probiotics in maintaining immune homeostasis
2022 - THIPE, VELAPHI C.; MENTOR, SHIREEN; LIMA, CAROLINE S.A.; FREITAS, LUCAS F.; FONSECA, ANA C.M.; NOGUEIRA, KAMILA M.; RODRIGUES, ADRIANA S.; BATISTA, JORGE G.S.; FERREIRA, ARYEL H.; LUGAO, ADEMAR B.
The immune system is a complex architecture of a collective and coordinated network regulated by various pathways to thermodynamically maintain immune homeostasis. The gut microbiota plays a pivotal role that offers significant stimuli (i.e., gut-brain, gut-lung, and gut-liver axis) for both innate and adaptive immunity, mediating immune and metabolic homeostasis. An intricate correlation between changes in the gut microbiota (dysbiosis) and common diseases/disorders have been attributed to the invasion of pathogens, constant use of antibiotics, and hypercytokinemia—a hallmark of immune homeostasis imbalance. These factors contribute to the severity of inflammatory diseases such as cardiovascular diseases, neurological disorders, and of late the coronavirus disease, Covid-19. Probiotics (Lactobacillus spp. and Bifidobacterium spp.) have been considered as alternative and/or adjuvant therapeutic in restoring the balance of gut microbiota for maintaining immune homeostasis and integrity. The probiotics catalyze dietary fibers and proteins to generate short-chain fatty acids and tryptophan to promote antiinflammatory cytokines, reduce epithelium permeability, reinforcing immunity in the gut mucosa, and regulating the systemic immune response. Herein, we review our overarching understanding of current applications of probiotics in amelioration of gut microbiome, and the improvement of gut barrier function and maintaining immune homeostasis. We also highlight clinical trials on probiotics with reported results for the treatment of inflammatory diseases. Additionally, the looming global Covid-19 pandemic makes it prudent to highlight the role of probiotics in both the innate and adaptive human immune responses, especially amid the Covid-19 vaccination paradigm.
Cu and Cu-based nanomaterials as nanofungicides
2022 - THIPE, VELAPHI C.; FREITAS, LUCAS F.; LIMA, CAROLINE S.A. de; NOGUEIRA, KAMILA M.; BATISTA, JORGE G.S.; FERREIRA, ARYEL H.; LUGAO, ADEMAR B.
Green nanotechnology through the production of copper and copper oxide nanoparticles (CuNPs and CuONPs, respectively) as nanofungicides brings forth the opportunity attributed to their antimicrobial properties in addition to Cu being an essential metal micronutrient that functions as a cofactor for many enzymatic activities in plants. Herein, we explore the use of CuNPs and CuONPs as nanofungicides against toxigenic fungi and their mechanism of action. We also highlight the green nanoagriculture and the ecotoxicology and safety of CuNPs and CuONPs as nanofungicides to significantly aid as agricultural breakthroughs because such approaches will provide realistic sustainable nano Cu-enabled products deemed safe for agricultural practices.
Desenvolvimento de nanopartículas de ouro (AuNPs) para teranóstica
2021 - RODRIGUES, ADRIANA de S.; LUGAO, ADEMAR B.; BATISTA, JORGE G. dos S.; KUCHINSKI, ADRIANA; FREITAS, LUCAS F. de; CRUZ, CASSIA P.C. da
The state of the art of theranostic nanomaterials for lung, breast, and prostate cancers
2021 - FREITAS, LUCAS F.; FERREIRA, ARYEL H.; THIPE, VELAPHI C.; VARCA, GUSTAVO H.C.; LIMA, CAROLINE S.A.; BATISTA, JORGE G.S.; RIELLO, FABIANE N.; NOGUEIRA, KAMILA; CRUZ, CASSIA P.C.; MENDES, GIOVANNA O.A.; RODRIGUES, ADRIANA S.; SOUSA, THAYNA S.; ALVES, VICTORIA M.; LUGAO, ADEMAR B.
The synthesis and engineering of nanomaterials offer more robust systems for the treatment of cancer, with technologies that combine therapy with imaging diagnostic tools in the so‐called nanotheranostics. Among the most studied systems, there are quantum dots, liposomes, polymeric nanoparticles, inorganic nanoparticles, magnetic nanoparticles, dendrimers, and gold nanoparticles. Most of the advantages of nanomaterials over the classic anticancer therapies come from their optimal size, which prevents the elimination by the kidneys and enhances their permeation in the tumor due to the abnormal blood vessels present in cancer tissues. Furthermore, the drug delivery and the contrast efficiency for imaging are enhanced, especially due to the increased surface area and the selective accumulation in the desired tissues. This property leads to the reduced drug dose necessary to exert the desired effect and for a longer action within the tumor. Finally, they are made so that there is no degradation into toxic byproducts and have a lower immune response triggering. In this article, we intend to review and discuss the state‐of‐the‐art regarding the use of nanomaterials as therapeutic and diagnostic tools for lung, breast, and prostate cancer, as they are among the most prevalent worldwide.
Hybrid gold-protein nanoparticles as radiosensitizers
2020 - FREITAS, L.F.; CRUZ, C.C. da; BATISTA, J.G.; VARCA, G.H.; LUGAO, A.B.; MATHOR, M.B.
Gold nanoparticles present unique optical properties which are dependent upon size and morphology, and consist on a differential interaction with radiation compared to the bulk material. Those nanoparticles can be modified in order to adjust their bioavailability and tissue-targeting, and one of the means to do so is by adsorbing one or more types of proteins onto their surface. Gamma radiation can be helpful in this regard, since it promotes intra- and intermolecular crosslinks in proteins and enables their adsorption onto the metallic nanoparticles’ surfaces. Here we present the results obtained for hybrid gold-protein nanoparticles as radiosensitizers. The nanoparticles were synthesized radiolytically by mixing 5 mmol L-1 NaAuCl4 with 1 mg mL-1 bovine serum albumin (BSA) or papain in the presence of 0.1 mol L-1 tert-butanol and 20% ethanol. The solutions were irradiated with 10 kGy in a multipurpose gamma irradiator (60Co source, 5 kGy per hour) for the radiolytic synthesis of the nanoparticles, and then the resulting red suspension was stored until use. 10^4 cells (MDA-MB-231 line) were seeded in 96-well plates and incubated with a 2:1 mixture of DMEM medium and nanoparticles suspension for 12 hours. Then, the wells were washed with sterile phosphate buffered saline, and fresh DMEM medium was added prior to irradiation in a gamma cell (60Co source, 0.6 kGy per hour) with 10, 30 and 50 Gy. 48 hours later, the cell viability was assessed by MTS assay. The results indicate that the radiation alone slightly stimulated the proliferation of the tumor cells, but this effect was more evident in the presence of gold-papain nanoparticles. The ablative effect due to radiosensitization was observed with 30 and 50 Gy for the cells incubated with gold-BSA nanoparticles, and 10 and 30 Gy for the cells incubated with gold-papain nanoparticles. This difference might be due to a more effective internalization or surface-attachment of nanoparticles when they are coated with papain, and one evidence for this assumption is the fact that the cell culture becomes red after the incubation with gold-papain nanoparticles. Therefore, protein-coated nanoparticles might be effective as radiosensitizers, depending on the coating and dose of radiation.
Green nanotechnology
2020 - BATISTA, J.G.; FREITAS, L.F.; CRUZ, C.C. da; LUGAO, A.B.; RODRIGUES, A.S.; SANTOS, L.O.; PIRES, M.A.
Cancer is among the diseases with the highest mortality rate, with more than 100 different types that occur due to mutations in the genetic material of cells. It is the third leading cause of death worldwide after cardiovascular and infectious diseases. In addition, the number of diseases caused by oxidative stress that results from an imbalance between the formation and neutralization of oxidizing species is increasingly perceived. Oxidative stress is initiated by free radicals and their interactions with biological macromolecules, such as proteins, lipids and DNA, healthy human cells and cause damage to proteins and DNA, with lipid peroxidation. These changes contribute to cancer, atherosclerosis, cardiovascular and inflammatory diseases. All cells are exposed to oxidative stress and therefore oxidation and free radicals play an important role in the development of cancer. Medicinal plants have a special place in cancer management. Several cancer researchers have been carried out studies using traditional medicinal plants, to discover new therapeutic agents that do not have side effects associated with chemotherapeutic agents. Studies using the extract of Annona muricata L., popularly known as araticum, have demonstrated potential anti-inflammatory and anticancer action, due to its antioxidant and immunological properties. The objective of the present work was to develop gold nanoparticles using Annona muricata L. dry extract and verify their physical-chemical characteristics, such as size, shape, and stability. The results obtained show that it is possible to synthesize gold nanoparticles with potential applications in medicine using the extract of araticum. Characterization was performed using the techniques of UV-Vis spectrophotometry, dynamic light scattering (DLS), transmission electron microscopy (TEM). The in vitro stability study of the gold nanoparticles synthesized with the araticum extract was carried out for thirty days. The nanoparticles showed to be stable in different media during this period and the monitoring was done by spectrophotometry.
Stability of gold nanoparticles in different ionic concentrations and pH
2020 - FREITAS, L.F.; CRUZ, C.C. da; BATISTA, J.G.; VARCA, G.H.; LUGAO, A.B.; PIRES, M.A.
There are several protocols for the synthesis of gold nanoparticles, and lately there is a trend for green methods in order to minimize the environmental impacts. The reduction of gold salts by epigallocatechin 3 gallate, for instance, generates stable and uniform nanoparticles without the use of toxic compounds, and so does the radiolytic synthesis protocol. For medical purposes, proteins like albumin and papain are useful coating agents, providing a better biological effectiveness. Here we present a comparison of different synthetic and protein coating protocols for gold nanoparticles regarding their stability in different NaCl concentrations and pH, aiming for the development of nanoparticles that are able to be administered in physiologic solutions to patients. The nanoparticles were synthesized via EGCG (2 mg mL 1) reduction of gold salt (5 mmol L 1) in phosphate buffer pH 7.0. Those nanoparticles were coated or not with albumin or papain (1 mg mL 1) using mercaptopropionic acid. Other protein coated gold nanoparticles were synthesized radiolytically by mixing 5 mmol L 1 NaAuCl4 with 1 mg mL 1 bovine serum albumin (BSA) or papain and 0.1 mol L 1 tert butanol. The solutions were irradiated with 10 kGy (60Co source, 5 kGy h 1) and the resulting suspensions were stored until use. The suspensions were added in 96 well plates to solutions with different pH and NaCl concentrations, and their absorption spectra were taken periodically to verify their stability. It was observed that BSA gold nanoparticles synthesized by both protocols were stable in concentrations of NaCl varying from 0.1% to 14.4% up to 72h. The papain gold nanoparticles synthesized by both protocols were stable in concentrations of NaCl varying from 0.1% to 14.4% up to 48h, but in 72h there was evidence of instability in the lowest and highest NaCl concentrations. The nanoparticles coated just with EGCG (without proteins) were stable in all NaCl concentrations and times, except in the highest concentration after 72h. Regarding the pH, BSA gold nanoparticles and papain gold nanoparticles synthesized radiolytically, as well as EGCG gold nanoparticles were stable at least in pH varying from 5 to 11, in all times analyzed. In conclusion, all the nanoparticles tested are able to be administered to patients in physiological solutions, which have pH around 7.4 and NaCl concentrations around 0.9%, without the risk of aggregation and loss of biological activity.
Nanotecnologia verde
2019 - BATISTA, J.G.S.; LUGAO, A.B.; DA CRUZ, C.C.; DE FREITAS, L.F.; SANTOS, L.O.; RODRIGUES, A.S.
O câncer está entre as doenças com maior índice de mortalidade, com mais de 100 tipos diferentes ocorrendo devido a mutações no material genético das células. É a terceira principal causa de morte em todo o mundo após doenças cardiovasculares e infecciosas. Além disso, percebe-se cada vez mais que muitas das doenças se devem ao “estresse oxidativo” que resulta de um desequilíbrio entre a formação e a neutralização de espécies oxidantes. O estresse oxidativo é iniciado pelos radicais livres, que buscam estabilidade através do pareamento de elétrons com macromoléculas biológicas, como proteínas, lipídios e DNA, em células humanas saudáveis e causam danos às proteínas e ao DNA, juntamente com a peroxidação lipídica. Essas mudanças contribuem para o câncer, aterosclerose, doenças cardiovasculares, envelhecimento e doenças inflamatórias. Todas as células são expostas ao estresse oxidativo e, portanto, a oxidação e os radicais livres desempenham um papel importante no desenvolvimento do câncer e na carcinogênese.Portanto, ainda estão sendo feitos esforços para procurar substâncias eficazes que ocorrem naturalmente e que possam impedir, desacelerar ou reverter o desenvolvimento do câncer. Plantas medicinais têm um lugar especial na gestão do câncer. Diversos estudos de pesquisa sobre o câncer foram realizados utilizando plantas medicinais tradicionais, em um esforço para descobrir novos agentes terapêuticos que não possuem efeitos secundários associados aos presentes agentes quimioterápicos. Estudos utilizando extrato de Annona muricata L., popularmente conhecida como araticum, demonstraram potencial ação anti-inflamatória e anticâncer, devido suas propriedades antioxidante e imunológica. O objetivo do presente trabalho foi sintetizar nanopartículas de ouro utilizando o extrato seco de Annona muricata L. e verificar suas propriedades físico-químicas, como tamanho, formato e estabilidade. E assim unir as propriedades do araticum com as das nanopartículas de ouro que possuem aplicações na terapia e diagnóstico de câncer. Os resultados obtidos, demonstram que é possível sintetizar nanopartículas de ouro com potencial aplicação na medicina utilizando o extrato de araticum. A caracterização foi realizada por meio das técnicas de espectrofotometria UV-Vis, espalhamento de luz dinâmico (DLS), microscopia eletrônica de transmissão (TEM). O estudo de estabilidade in vitro foi realizado misturando-se a solução de nanopartículas de ouro com NaCl, histidina, cisteína, BSA, pH 5, 7 e 9. As nanopartículas apresentaram tamanho médio de 15 nm por TEM e tamanho hidrodinâmico médio de 30 nm por DLS. No teste de estabilidade in vitro, as nanopartículas de ouro sintetizadas com o extrato seco de araticum apresentaram estabilidade em todos os meios testados por até 14 dias, não havendo diminuição na absorbância no comprimento de 525 nm, que é característico do dipolo gerado pela ressonância plasmônica de superfície em nanopartículas de ouro.