Publications by authors named "Aline Oliveira da Silva de Barros"

10 Publications

  • Page 1 of 1

Distinct Methodologies to Produce Capped Mesoporous Silica with Hydroxyapatite and the Influence in Intracellular Signaling as Cytotoxicity on Human Umbilical Vein Endothelial Cells.

Bioengineering (Basel) 2021 Sep 12;8(9). Epub 2021 Sep 12.

Laboratory of Synthesis of Novel Radiopharmaceuticals and Nanoradiopharmacy, Nuclear Engineering Institute, Brazilian Nuclear Energy Commission, Rio de Janeiro 21941906, Brazil.

Mesoporous silica has unique properties such as controllable mesoporous structure and size, good biocompatibility, high specific surface area, and large pore volume. For that reason, this material has been broadly functionalized for biomedical applications, such as optical imaging, magnetic resonance imaging (MRI), positron emission tomography (PET), computed tomography (CT), ultrasound imaging, and widely employed as drug delivery systems. In this study, we synthesized fiber-type mesoporous silica capped with hydroxyapatite (ordered SiO-CaO-PO mesoporous silica). Its biological activity was evaluated through a cellular and molecular approach using HUVEC cell culture. Two distinct methodologies have produced the ordered SiO-CaO-PO mesoporous silica: (i) two-step Ca-doped silica matrix followed by hydroxyapatite crystallization inside the Ca-doped silica matrix and (ii) one-step Ca-doped silica matrix formed with the hydroxyapatite crystallization. Further analysis included: elemental analysis, transmission, scanning electron microscopy images, Small and Wide-Angle X-ray Diffraction analysis, Fourier Transform Infrared, and in vitro assays with HUVEC (cytotoxicity and immunoblotting). The hydroxyapatite capping methodology significantly affected the original mesoporous material structure. Furthermore, no cellular or molecular effect has been observed. The promising results presented here suggest that the one-step method to obtain hydroxyapatite capped mesoporous silica was effective, also demonstrating that this material has potential in biomedical applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/bioengineering8090125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465229PMC
September 2021

Preliminary studies on drug delivery of polymeric primaquine microparticles using the liver high uptake effect based on size of particles to improve malaria treatment.

Mater Sci Eng C Mater Biol Appl 2021 Sep 25;128:112275. Epub 2021 Jun 25.

Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, Laboratory of Novel Radiopharmaceuticals and Nano-radiopharmacy, Rio de Janeiro 21941906, Brazil; Zona Oeste State University, Laboratory of Nanoradiopharmaceuticals and Radiopharmacy, Rio de Janeiro 23070200, Brazil. Electronic address:

Malaria is the most common parasitic disease around the world, especially in tropical and sub-tropical regions. This parasitic disease can have a rapid and severe evolution. It is transmitted by female anopheline mosquitoes. There is no reliable vaccine or diagnostic test against malaria; instead, Artesunate is used for the treatment of severe malaria and Artemisinin is used for uncomplicated falciparum malaria. However, these treatments are not efficient against severe malaria and improvements are needed. Primaquine (PQ) is one of the most widely used antimalarial drugs. It is the only available drug to date for combating the relapsing form of malaria. Nevertheless, it has severe side effects. Particle drug-delivery systems present the ability to enhance the therapeutic properties of drugs and decrease their side effects. Here, we report the development of Polymeric Primaquine Microparticles (PPM) labeled with 99mTc for therapeutic strategy against malaria infection. The amount of primaquine encapsulated into the PPM was 79.54%. PPM presented a mean size of 929.47 ± 37.72 nm, with a PDI of 0.228 ± 0.05 showing a homogeneous size for the microparticles and a monodispersive behavior. Furthermore, the biodistribution test showed that primaquine microparticles have a high liver accumulation. In vivo experiments using mice show that the PPM treatments resulted in partial efficacy and protection against the development of the parasite compared to free Primaquine. These results suggest that microparticles drug delivery systems of primaquine could be a possible approach for malaria prevention and treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msec.2021.112275DOI Listing
September 2021

Biomedical application of graphitic carbon nitrides: tissue deposition, induction of reactive oxygen species (ROS) and cell viability in tumor cells.

Nanotechnology 2021 Aug 2;32(43). Epub 2021 Aug 2.

Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, Laboratory of Nanoradiopharmacy and Synthesis of New Radiopharmaceuticals, Rio de Janeiro-RJ, 21941906, Brazil.

The urgency for new materials in oncology is immediate. In this study we have developed the g-CN, a graphitic-like structure formed by periodically linked tris-s-triazine units. The g-CNhas been synthesized by a simple and fast thermal process. XRD has shown the formation of the crystalline sheet with a compacted structure. The graphite-like structure and the functional groups have been shown by Raman and FTIR spectroscopy. TEM image and AFM revealed the porous composed of five or six C-N layers stacked. DRS and Photoluminescence analyses confirmed the structure with band gap of 2.87 eV and emission band at 448 nm in different wavelengths excitation conditions. The biological results showed inhibitory effect on cancer cell lines and non-toxic effect in normal cell lines. To the best of our knowledge, this is the first work demonstrating the cytotoxic effects of 2D g-CNin a cancer cell line, without any external or synergistic influence. The biodistribution/tissue accumulation showed that g-CNpresent a tendency to accumulation on the lung in the first 2 h, but after 24 h the profile of the biodistribution change and it is found mainly in the liver. Thus, 2D-g-CNshowed great potential for the treatment of several cancer types.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1088/1361-6528/ac1540DOI Listing
August 2021

Graphene: Insights on Biological, Radiochemical and Ecotoxicological Aspects.

J Biomed Nanotechnol 2021 Jan;17(1):131-148

Graphene, including graphene quantum dots, its oxide and unoxidized forms (pure graphene) have several properties, like fluorescence, electrical conductivity, theoretical surface area, low toxicity, and high biocompatibility. In this study, we evaluated genotoxicity ( analysis using the functional density theory-FDT), cytotoxicity (human glioblastoma cell line), pharmacokinetics, impact on microcirculation and cell internalization assay. It was also radiolabeled with lutetium 177 (177Lu), a beta emitter radioisotope to explore its therapeutic use as nanodrug. Finally, the impact of its disposal in the environment was analyzed using ecotoxicological evaluation. FDT analysis demonstrated that graphene can construct covalent and non-covalent bonds with different nucleobases, and graphene oxide is responsible for generation of reactive oxygen species (ROS), corroborating its genotoxicity. On the other hand, non-cytotoxic effect on glioblastoma cells could be demonstrated. The pharmacokinetics analysis showed high plasmatic concentration and clearance. Topical application of 0.1 and 1 mg/kg of graphene nanoparticles on the hamster skinfold preparation did not show inflammatory effect. The cell internalization assay showed that 1-hour post contact with cells, graphene can cross the plasmatic membrane and accumulate in the cytoplasm. Radio labeling with 177Lu is possible and its use as therapeutic nanosystem is viable. Finally, the ecotoxicity analysis showed that exposed to graphene showed pronounced uptake and absorption in the nauplii gut and formation of ROS. The data obtained showed that although being formed exclusively of carbon and carbon-oxygen, graphene and graphene oxide respectively generate somewhat contradictory results and more studies should be performed to certify the safety use of this nanoplatform.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1166/jbn.2021.3006DOI Listing
January 2021

Dual Encapsulated Dacarbazine and Zinc Phthalocyanine Polymeric Nanoparticle for Photodynamic Therapy of Melanoma.

Pharm Res 2021 Feb 18;38(2):335-346. Epub 2021 Feb 18.

Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, Rua Helio de Almeida, 75, Ilha do Fundão, Rio de Janeiro, Brazil.

Purpose: Melanoma is an invasive and very aggressive skin cancer due to its multi-drug resistance that results in poor patient survival. There is a need to test new treatment approaches to improve therapeutic efficacy and reduce side effects of conventional treatments.

Methods: PLA/PVA nanoparticles carrying both Dacarbazine and zinc phthalocyanine was produced by double emulsion technique. The characterization was performed by dynamic light scattering and atomic force microscopy. In vitro photodynamic therapy test assay using MV3 melanoma cells as a model has been performed. In vitro cell viability (MTT) was performed to measure cell toxicity of of nanoparticles with and without drugs using human endothelial cells as a model. The in vivo assay (biodistribution/tissue deposition) has been performed using radiolabeled PLA/PVA NPs.

Results: The nanoparticles produced showed a mean diameter of about 259 nm with a spherical shape. The in-vitro photodynamic therapy tests demonstrated that the combination is critical to enhance the therapeutic efficacy and it is dose dependent. The in vitro cell toxicity assay using endothelial cells demonstrated that the drug encapsulated into nanoparticles had no significant toxicity compared to control samples. In-vivo results demonstrated that the drug loading affects the biodistribution of the nanoparticle formulations (NPs). Low accumulation of the NPs into the stomach, heart, brain, and kidneys suggested that common side effects of Dacarbazine could be reduced.

Conclusion: This work reports a robust nanoparticle formulation with the objective to leveraging the synergistic effects of chemo and photodynamic therapies to potentially suppressing the drug resistance and reducing side effects associated with Dacarbazine. The data corroborates that the dual encapsulated NPs showed better in-vitro efficacy when compared with the both compounds alone. The results support the need to have a dual modality NP formulation for melanoma therapy by combining chemotherapy and photodynamic therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11095-021-02999-wDOI Listing
February 2021

Radioactive gold nanocluster (198-AuNCs) showed inhibitory effects on cancer cells lines.

Artif Cells Nanomed Biotechnol 2020 Dec;48(1):1214-1221

Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, Rio de Janeiro, Brazil.

Cancer is a global epidemic disease responsible for over ten millions death worldwide. The early diagnosis and the precise treatment with reduced adverse reactions are the main goal worldwide. In this study, we produced, characterized and evaluated ( in three different cancer cell lines (protaste, breast and melanoma) a radioactive gold nanocluster (R-AuNC) (Au25(Capt)18). The pharmacokinetics as the influence in the ABC transporter (MRP1 Efflux Transporter Protein) was also evaluated. The results showed that R-AuNC (Au25(Capt)18) are capable to kill the cancer cells lines of protaste, breast and melanoma. The pharmacokinetics showed a fast clearance and great volume of distribution, confirming the use of R-AuNC as nanomedicine for cancer treatment. Finally, the ABC transporter assay corroborated that the R-AuNC (Au25(Capt)18) has no risk of being pumped out of cells by this efflux transporter. The results validate the use of gold nanoparticles as therapeutic nanomedicine for cancer treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21691401.2020.1821698DOI Listing
December 2020

Molecular and Cellular Risk Assessment of Healthy Human Cells and Cancer Human Cells Exposed to Nanoparticles.

Int J Mol Sci 2019 Dec 28;21(1). Epub 2019 Dec 28.

Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, Rio de Janeiro 21941906, Brazil.

Nanodrugs have in recent years been a subject of great debate. In 2017 alone, almost 50 nanodrugs were approved for clinical use worldwide. Despite the advantages related to nanodrugs/nanomedicine, there is still a lack of information regarding the biological safety, as the real behavior of these nanodrugs in the body. In order to better understand these aspects, in this study, we evaluated the effect of polylactic acid (PLA) nanoparticles (NPs) and magnetic core mesoporous silica nanoparticles (MMSN, of 1000 nm and 50 nm, respectively, on human cells. In this direction we evaluated the cell cycle, cytochemistry, proliferation and tubulogenesis on tumor cells lines: from melanoma (MV3), breast cancer (MCF-7, MDA-MB-213), glioma (U373MG), prostate (PC3), gastric (AGS) and colon adenocarcinoma (HT-29) and non-tumor cell lines: from human melanocyte (NGM), fibroblast (FGH) and endothelial (HUVEC), respectively. The data showed that an acute exposure to both, polymeric nanoparticles or MMSN, did not show any relevant toxic effects on neither tumor cells nor non-tumor cells, suggesting that although nanodrugs may present unrevealed aspects, under acute exposition to human cells they are harmless.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21010230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981945PMC
December 2019

Octreotide Nanoparticles Showed Affinity for In Vivo MIA Paca-2 Inducted Pancreas Ductal Adenocarcinoma Mimicking Pancreatic Polypeptide-Secreting Tumor of the Distal Pancreas (PPoma).

Pharm Res 2019 Aug 5;36(10):143. Epub 2019 Aug 5.

Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, Rio de Janeiro, Brazil.

Purpose: Pancreatic Polypeptide-secreting tumor of the distal pancreas (PPoma) is a rare, difficult and indolent type of cancer with a survival rate of 5-year in only 10% of all cases. The PPoma is classified as a neuroendocrine tumor (NET) not functioning that overexpresses SSTR 2 (somatostatin receptor subtype 2). Thus, in order to improve the diagnosis of this type of tumor, we developed nanoparticulate drug carriers based on poly-lactic acid (PLA) polymer loaded with octreotide and radiolabeled with Technetium-99 m (Tc).

Methods: PLA/PVA octreotide nanoparticles were developed by double-emulsion technique. These nanoparticles were characterized by Atomic Force Microscopy (AFM) and Dynamic Light Scattering (DLS) and radiolabeled with 99mTc by the direct via forming Tc-PLA/PVA octreotide nanoparticles. The safety of these nanosystems was evaluated by the MTT cell toxicity assay and their in vivo biodistribution was evaluated in xenografted inducted animals.

Results: The results showed that a 189 nm sized nanoparticle were formed with a PDI of 0,097, corroborating the monodispersive behavior. These nanoparticles were successfully radiolabeled with 99mTc showing uptake by the inducted tumor. The MTT assay corroborated the safety of the nanosystem for the cells.

Conclusion: The results support the use of this nanosystem (Tc-PLA/PVA octreotide nanoparticles) as imaging agent for PPoma. Graphical Abstract Polypeptide-Secreting Tumor of the Distal Pancreas (PPoma) Radiolabeled Nanoparticles for Imaging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11095-019-2678-4DOI Listing
August 2019

Graphene quantum dots unraveling: Green synthesis, characterization, radiolabeling with 99mTc, in vivo behavior and mutagenicity.

Mater Sci Eng C Mater Biol Appl 2019 Sep 24;102:405-414. Epub 2019 Apr 24.

Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, Rua Helio de Almeida 75, Ilha do Fundão, CEP 21941-614 Rio de Janeiro, Brazil; Zona Oeste State University, Laboratory of Radiopharmacy and Nanoradiopharmaceuticals, Campo Grande, Rio de Janeiro, Brazil. Electronic address:

Graphene is one of the crystalline forms of carbon, along with diamond, graphite, carbon nanotubes, and fullerenes, and is considered as a revolutionary and innovating product. The use of a graphene-based nanolabels is one of the latest and most prominent application of graphene, especially in the field of diagnosis and, recently, in loco radiotherapy when coupled with radioisotopes. However, its biological behavior and mutagenicity in different cell or animal models, as well as the in vivo functional activities, are still unrevealed. In this study we have developed by a green route of synthesizing graphene quantum dots (GQDs) and characterized them. We have also developed a methodology for direct radiolabeling of GQDs with radioisotopes.Finally; we have evaluated in vivo biological behavior of GQDs using two different mice models and tested in vitro mutagenicity of GQDs. The results have shown that GQDs were formed with a size range of 160-280 nm, which was confirmed by DRX and Raman spectroscopy analysis, corroborating that the green synthesis is an alternative, environmentally friendly way to produce graphene. The radiolabeling test has shown that stable radiolabeled GQDs can be produced with a high yield (>90%). The in vivo test has demonstrated a ubiquitous behavior when administered to healthy animals, with a high uptake by liver (>26%) and small intestine (>25%). Otherwise, in an inflammation/VEGF hyperexpression animal model (endometriosis), a very peculiar behavior of GQDs was observed, with a high uptake by kidneys (over 85%). The mutagenicity test has demonstrated A:T to G:C substitutions suggesting that GQDs exhibits mutagenic activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msec.2019.04.058DOI Listing
September 2019

In loco retention effect of magnetic core mesoporous silica nanoparticles doped with trastuzumab as intralesional nanodrug for breast cancer.

Artif Cells Nanomed Biotechnol 2018 19;46(sup3):S725-S733. Epub 2018 Nov 19.

a Brazilian Nuclear Energy Commission , Nuclear Engineering Institute , Rio de Janeiro , Brazil.

Breast cancer is women's most common type of cancer, with a global rate of over 522,000 deaths per year. One of the main problems related to breast cancer relies in the early detection, as the specialized treatment. In this direction was developed, characterized and tested in vivo a smart delivery system, based on radiolabelled magnetic core mesoporous silica doped with trastuzumab as intralesional nanodrug for breast cancer imaging and possible therapy. The results showed that nanoparticles had a size of 58.9 ± 8.1 nm, with specific surface area of 872 m/g and pore volume of 0.85 cm/g with a pore diameter of 3.15 nm. The magnetic core mesoporous silica was efficiently labelled with 99mTc (97.5% ±0.8) and doped >98%. The cytotoxicity assay, demonstrated they are safe to use. The data were corroborated with the IC50 result of: 829.6 µg ± 43.2. The biodistribution showed an uptake by the tumour of 7.5% (systemic via) and 97.37% (intralesional) with less than 3% of these nanoparticles absorbed by healthy tissues. In a period 6-h post-injection, no barrier delimited by the tumour was crossed, corroborating the use as intralesional nanodrug.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21691401.2018.1508030DOI Listing
June 2019
-->