JORGE GABRIEL DOS SANTOS BATISTA

JORGE GABRIEL DOS SANTOS BATISTA

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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.
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.
Comparison between gold nanoparticles synthesized by radiolysis and by EGCG-driven gold reduction
2020 - FREITAS, LUCAS F. de; CRUZ, CASSIA P.C. da; CAVALCANTE, ADRIANA K.; BATISTA, JORGE G. dos S.; VARCA, GUSTAVO H.C.; MATHOR, MONICA B.; LUGAO, ADEMAR B.
Radiolytic synthesis and phytochemical-driven gold reduction for the generation of nanoparticles are successful examples of Green Chemistry applied for nanomaterials. The present work compares these two green approaches focusing on hydrodynamic size, stability over time, optical properties and toxicity in NIH 3T3 (ATCC® CRL- 1658™) cells and Danio rerio (Zebra Fish). The radiolytic synthesis was performed by mixing 1 mM NaAuCl4; polyvinyl pyrrolidone 0.5%, AgNO3 6×10−5 M, propan-2-ol 0.2 M and acetone 0.06 M, followed by irradiation at 15 kGy (5 kGy h−1, 60Co source). The EGCG-functionalized nanoparticles were synthesized by mixing 1.6 mM of Au with 0.8 mM of EGCG in phosphate buffer (10 mM) for 2 h. Both methods yield the formation of gold nanoparticles featuring plasmon resonance bands at 520–530 nm, polydispersity above 0.3 was relevant only for the radiolytic protocol. Regarding stability over time, after 30 days, the nanoparticles synthesized radiolytically presented no relevant size changes, while some aggregation was observed for the EGCG-particles. The same nanoparticles demonstrated a lack of stability in high ionic strength medium. Slight toxicity was observed for the EGCG-nanoparticles in Danio rerio, with an IC50 calculated as 40.49%, while no IC50 was established within the concentration range of radiolysis-AuNPs used in this study. In conclusion, both green methods generated nanoparticles with good control of size and optical properties, especially via reduction by EGCG. However, the stability and toxicity results were found to be more promising for the radiolytically synthesized gold nanoparticles.
Protein crosslinking onto gold nanoparticles by gamma radiation
2017 - VARCA, GUSTAVO H.C.; BARROS, JANAINA A.G.; BATISTA, JORGE G.S.; SASOUNIAN, RAFAELA; SILVA, GUSTAVO T.M.; ZAMARION, VITOR M.; KATTI, KATTESH V.; LUGAO, ADEMAR B.
The use of gold nanoparticles for diagnosis and treatment of cancer has received great attention over the last decade. Particularly, the possibility to use them for theranostics has increased the interest in the medical and scientific community. Weak technological aspects are related to the low biological affinity and non-specific toxicity. The use of albumin is of highlighted interest as albumin has been associated to inorganic particles to overcome biopharmaceutical challenges, including site-specific delivery and other biopharmaceutical advantages. The current work addresses the use of radiation and its effects over the crosslinking of bovine serum albumin onto gold nanoparticles. The idea of crosslinking the albumin onto gold surface aims to improve the stability of the protein layer onto gold nanoparticles in biological systems. Gold nanoparticles were synthesized by green technology using resveratrol and albumin capping was performed by physiosorption followed by irradiation at doses of 2.5, 5, 7.5, 10 and 15 kGy using 60Co as a radioactive source. Nanoparticle properties were assessed by dynamic light scattering, UV/Vis spectrophotometry and transmission electron microscopy. Protein crosslinking was monitored by fluorescence studies and stability of the nanoparticles was evaluated by zeta potential and titration with sodium chloride. The results evidenced the formation of a protein layer onto gold nanoparticles and revealed a protein crosslinking by means of bityrosine as a function of irradiation dose. Stability was considerably improved by the presence of the protein layer and the crosslinked protein layer.
An overview of the synthesis of gold nanoparticles using radiation technologies
2018 - FREITAS, LUCAS F. de; VARCA, GUSTAVO H.C.; BATISTA, JORGE G. dos S.; LUGAO, ADEMAR B.
At a nano-level, optical properties of gold are unique and gave birth to an emerging platform of nanogold-based systems for diverse applications, because gold nanoparticle properties are tunable as a function of size and shape. Within the available techniques for the synthesis of gold nanoparticles, the radiolytic synthesis allows proper control of the nucleation process without the need for reducing agents, in a single step, combined or not with simultaneous sterilization. This review details and summarizes the use of radiation technologies for the synthesis and preparation of gold nanoparticles concerning fundamental aspects, mechanism, current pathways for synthesis and radiation sources, as well as briefly outlines final applications and some toxicity aspects related to nanogold-based systems.
In vitro and in vivo toxicity evaluation of resveratrol assisted gold nanoparticles
2017 - BARROS, JANAINA A.G.; MAZIERO, JOANA S.; MAMEDE, FERNANDA C.S.; CAVALCANTE, ADRIANA K.; ROGERO, SIZUE O.; BATISTA, JORGE G.S.; VARCA, GUSTAVO H.C.; ROGERO, JOSE R.; LUGAO, ADEMAR B.
Gold nanoparticles (AuNP) are being investigated for diagnostic and therapeutic nanomedicines considering their low toxicity and stability against oxidation, among other features. The increasing production and use of AuNP can result in release of them into aquatic environment and the impacts on the aquatic organisms are not clear and the safety of AuNPs are still under investigation. This work aimed analyze the toxicity of resveratrol assisted AuNP synthesized in buffer phosphate pH 7.0 with approximately 47 nm in DLS and 15 nm in TEM analysis and gold ionic solution (Au+3). Cytotoxicity by neutral red uptake method and acute ecotoxicological assay on Daphnia similis were used. AuNP presented no cytotoxicity up to 246 mg L-1 while Au+3 showed IC50=7.95 mg L-1. AuNP CE50 was 113.15 mg L-1 and for Au+3 0.05 mg L-1. More studies can be conducted for the determination of safety ionic Au+3 and AuNP concentrations in aquatic environment.
Radiation-induced "one pot" synthesis for cell therapies
2017 - LUGAO, ADEMAR B.; FAZOLIN, GABRIELA N.; VARCA, GUSTAVO H.C.; SANTOS, JORGE G.; BARROS, JANAINA; FUCASE, TAMARA; SANTOS, JONNATAN J.; LEAL, JESSICA; GRASSELLI, MARIANO; KATTI, KATTESH V.
The dream of Marie Curie lab’s expressed by Regaud and Lacassagne in 1927 was to administer radiations with penetration range of molecular dimensions to the organism and selectively fixed in the protoplasm of cells one seeks to destroy. Gold nanoparticles can be employed as a radiation sensitizer by utilizing mainly Auger effect and photoelectrons. Auger electrons are released in large numbers with low kinetic energy therefore these electrons damage cells over a very short range: less than the size of a single cell, on the order of nanometers. Gold-198 is a beta and gamma emitter can be employed for therapy as well as diagnostic. The radioactive properties of gold include: Au (βmax=0.96 MeV; t1/2 = 2.7 days) and Au (βmax =0.46 MeV; t1/2 = 3.14 days), making it a strong candidate for theranostics. However, Gold or Gold-198 need to internalize selectively in tumor cells. Conjugation with proteins and peptides can make them very selective. While radioactive nanoparticles can offer a much higher dose payload than ions for therapy and diagnostic, in addition to the huge surface to bind targeting species presented by the nanoparticles, functionalization with proteins may potentially increases the particle uptake by tumors or tissues. Albumin and Papain features a set of characteristics that assure applications as natural drug carriers with particular attractive properties in oncology. Albumin may be easily crosslinked and engineered towards loading of large number of hydrophobic molecules as well as hydrophilic ones. They can be bound in a reversible way and the delivery controlled by endogenous mechanism. Alternatively to conventional systems, albumin can be crosslinked by radiation in such way that dialdehydes or toxic chemicals are totally avoided . Conjugation of such materials with sugars, peptides, antibodies, proteins among others is routinely used nowadays for targeting. The main purpose of this work was the development of one pot in situ synthesis of radioactive gold 198 nanoparticle encapsulated by albumin for application in cancer Theranostics. While crosslinked albumin may provide a nontoxic coating on AuNPs with a controllable hydrodynamic diameter, conventional AuNP can be activated by nuclear reactor to produce AuNP. The gamma or beta radiation originated from the gold nanoparticle was used to crosslink the Albumin layer. The use of a radioactive particle able to emit radiation for crosslinking of the Albumin layer and simultaneous theranostic application was tried for the first time. The elegant procedure and simplicity of the production process combined with the properties of Au and the safety of AuNP/BSA make this new particle an exciting advancement in cancer therapy and diagnosis. Gold conjugated protein nanoparticles and protein nanoparticles itself were also produced in an radiation induced one pot process. Crosslinking and protein damage werea cessed by different techniques.
Evaluation of the in vitro and in vivo toxicity of gold nanoparticles synthesized by green nanotechnology
2017 - BATISTA, JORGE G.S.; BARROS, JANAINA A.G.; VARCA, GUSTAVO H.C.; ROGERO, SIZUE O.; CAVALCANTE, ADRIANA K.; MAZIERO, JOANA S.; ROGERO, JOSE R.; LUGAO, ADEMAR B.
Researchers and laboratories around the world have studied gold nanoparticles. In medicine, several studies demonstrate the applicability of gold nanoparticles (AuNPs) in the treatment and diagnosis of cancer. Green nanotechnology uses phytochemical agents to synthesize and stabilize nanoparticles. The phytochemical epigallocatechin-gallate (EGCG) reduces and stabilize gold nanoparticles by functionalizing the surface of the molecule. Such chemical groups allow binding to overexpressed receptors on some types of tumors as demonstrated in studies performed with PC3 prostate cancer cells. With the advancement of nanotechnology, a large number of nanoparticles are produced on a daily basis. However apart from their possible applications it is necessary to evaluate the environmental impact of these molecules as well as find ways for proper disposal. The embryonic zebrafish (Danio rerio) trial has recently emerged as an interesting method for evaluating in vivo nanotoxicity providing a more complex system analysis than in typical cell cultures and less expensive if compared to large-scale biocompatibility studies performed in rats and mice. The objective of this study was to evaluate the in vitro and in vivo toxicity of EGCG-AuNPs by means of the cytotoxicity by neutral red uptake methodology according to the International Standard Organization [ISO 10993-5, 2009] and in vivo test based on the OECD guideline on Fish Embryo Toxicity Test (FET) (OECD, 2013). The spectrophotometric band at 535 nm observed is characteristic of the formation of AuNPs. Nanoparticles synthesized with EGCG presented a size of 32 ± 4 nm as determined by transmission electron microscopy and the hydrodynamic diameter of these particles was about 60 ± 18 nm obtained by dynamic light scattering. The EGCG-AuNPs showed no cytotoxicity up to 4.2 μg.L-1. In the FET test regarding the acute ecotoxicity assay the LC50/96 hours revealed no toxicity at concentrations up to 1.8 mM.
State of the art and current advances on protein cross-linking by irradiation: protein based nanocarriers and bioactive nanoparticles
2017 - VARCA, G.H.C.; MOHAMED, L.B.; FAZOLIN, G.N.; BATISTA, J.G.D.S.; QUEIROZ, R.G.; LUGAO, A.B.; NAVARRO MARQUES, F.A.; FERREIRA, A.H.
The highlighted role of protein and peptide based delivery systems relies upon the possibility to develop biocompatible drug carriers featuring site specific delivery, biological affinity among unique advantages. Recently, a technique for protein nanostructuring by the use of radiation has been recently reported by our group. Advantages of the use of radiation over conventional methods are related to the possibility to achieve protein cross-linking and sterilization in a single step, as well as the capacity to allow the design of nanocarriers without the need of monomers or toxic cross-linkers. This work reports the use of high energy irradiation towards the design of size-controlled protein-based nanocarriers and bioactive nanoparticles, using bovine serum albumin (BSA) and papain as model protein and protease, respectively, including the state of the art and current advances of the technology. The technique implies on protein desolvation/solvation techniques followed by cross-linking by EB radiation or -irradiation alone, although nanoparticles were also achieved in absence of the cosolvents. Size-controlled BSA nanocarriers were manufactured up to 80 nm and papain bioactive nanoparticles up to 12 nm, as determined by dynamic light scattering. Nanocarrier morphology was evaluated by and negative staining transmission electron microscopy. Protein cross-linking and changes in aromatic the amino acids were evaluated by fluorescence measurements. Biocompatibility experimentswere also performed by means of cytotoxicity and cytokines production. The potential of the systems for the delivery of radiopharmaceuticals or chemotherapeutic agents were also assayed, using technetium or Paclitaxel respectively. In conclusion, the technique allowed the production of biocompatible and bioactive protein nanoparticles suitable for the administration of radiopharmaceuticals and chemotherapeutic agents.