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Item GMEH - Software de Gerenciamento de Manutenção de Equipamentos Hospitalares(2021-12-17) Ferraz, William de Carvalho; Castilho, Maiara Lima; Raniero, Leandro José; Ferreira, Hélio Lourenço EsperidiãoItem Gold nanoparticles conjugated with epidermal growth factor and gadolinium for precision delivery of contrast agents in magnetic resonance imaging(Springer-Verlag London Ltd.) Queiroz, Marinho de; Veriato, Thaís da Silva; Raniero, Leandro José; Castilho, Maiara LimaThe utilization of contrast agents in magnetic resonance imaging (MRI) has become increasingly important in clinical diagnosis. However, the low diagnostic specificity of this technique is a limiting factor for the early detection of tumors. To develop a new contrast agent with a specific target for early stage tumors, we present the synthesis and characterization of a nanocontrast composed of gold nanoparticles (AuNPs), gadopentetic acid (Gd-DTPA), and epidermal growth factor (EGF). Carbodiimide-based chemistry was utilized to modify Gd-DTPA for functionalization with AuNPs. This resulted in the formation of the Au@Gd-EGF nanocontrast. The relaxation rate (1/T1) of the nanocontrast was analyzed using MRI, and cytotoxicity was determined based on cell viability and mitochondrial activity in a human breast adenocarcinoma cell line. Fourier-transform infrared spectroscopy analysis confirmed the effectiveness of carbodiimide in the formation of the Gd-DTPA-cysteamine complex in the presence of bands at 930, 1042, 1232, 1588, and 1716 cm-1. The complexes exhibited good interactions with the AuNPs. However, the signal intensity of the Au@Gd-EGF nanocontrast was lower than that of the commercial contrast agent because the r1/r2 relaxivities of the Gd-DTPA-based contrast agents were lower than those of the gadoversetamide-based molecules. The Au@Gd-EGF nanocontrast agent exhibited good biocompatibility, low cytotoxicity, and high signal intensity in MRI with active targeted delivery, suggesting significant potential for future applications in the early diagnosis of tumors.Item Antibacterial activity of silver nanoparticles functionalized with amikacin applied against multidrug-resistant acinetobacter baumannii(Elsevier) Camargo, Larissa de Oliveira; Fontoura, Inglid; Veriato, Thaís da Silva; Raniero, Leandro José; Castilho, Maiara LimaBackground: Multidrug-resistant bacteria are one of the world's biggest health problems; therefore, improving the spectrum of action of antibiotics could be necessary to reverse this situation. Amikacin and silver salts have well-known antimicrobial properties. However, both drugs lost their effectiveness against some bacteria, such as Acinetobacter baumannii. This work aims to develop a nanodrug from silver nanoparticles (AgNPs) functionalized with Amikacin against multidrug-resistant Acinetobacter baumannii. Methods: AgNPs were produced using the bottom-up methodology and functionalized with Amikacin modified by the carbodiimide-based chemistry, forming AgNPs@Amikacin. Susceptibility tests were performed using Amikacin-resistant Acinetobacter baumannii strains to assess the bacteriostatic and bactericidal potential of the developed nanodrug. The clinical strains were induced to form a biofilm, and biomass quantification and the metabolic activity were determined. Results: The AgNPs have a hydrodynamic diameter of the particles with a bimodal distribution, with a size of 37.84 nm. The FT-IR spectrum of AgNPs@Amikacin exhibits vibrational modes corresponding to Amikacin, confirming the conjugation to AgNPs. Susceptibility testing demonstrated a minimal inhibitory and bactericidal concentration of < 0.5 µg/mL. The AgNPs@Amikacin reduced the biofilm metabolic activity of Acinetobacter baumannii at rates ≥ 50%, characterized by the minimal biofilm inhibition concentrations. Conclusions: Results demonstrate a promising development of a new nanodrug with lower concentrations, less toxicity, and greater efficacy against multidrug-resistant Acinetobacter baumannii.Item Specific nanomarkers fluorescence: in vitro analysis for EGFR overexpressed cells in triple-negative breast cancer and malignant glioblastoma(Elsevier) Vieira, Paula Fonseca Antunes; Jesus, Viviane Paula dos Santos; Cândido, Marcela Aparecida; Pacheco-Soares, Cristina; Castilho, Maiara Lima; Raniero, Leandro JoséBackground: Epidermal Growth Factor Receptor (EGFR receptor) is encoded by the EGFR gene. EGFR receptor signaling pathways are activated by EGF protein, regulating cell actions. Overexpression of EGFR receptor may be linked to malignancies with a poor prognosis. As a result, EGFR receptor is being studied for a variety of tumor diagnostics, spurring the development of innovative approaches to increase quality and efficiency. Nanomaterials can recognize cancer cells by specifically targeting of molecular pathways, underscoring the importance of nanomedicine. In this study, we synthesized EGFR-specific nanomarkers by functionalizing EGF protein and Chlorin e6 in gold nanoparticles. These nanoparticles use active targeting to deliver EGF protein to EGFR receptor, and Chlorin e6 serves as a fluorescent marker molecule Methods: Nanomarkers were examined in vitro in MDA-MB-468 and M059J cell lines. Confocal microscopy and flow cytometry were used to examine the distribution, uptake, internalization, and fluorescence intensity of nanomarkers in vitro Results: The results show that both lines examined accumulate nanomarkers. However, MDA-MB-468 had the highest intensity due to its EGFR receptor overexpression properties Conclusion: The findings point to ideal properties for detecting EGFR receptor overexpressed cells.Item Gold nanoparticles associated with temozolomide for glioblastoma Multiforme Treatment(CDRR Editors) Gialluca, Vanessa Dias; Lima, Vitor Gabriel Poli de; Caixeta, Aloísio; Castilho, Maiara Lima; Raniero, Leandro JoséMalignant neoplasms represents a group of diseases that features, as a characteristic, the genetic differentiation of the original tissue, leading to the disordered growth of cells, invading normal tissues and organs. Among the most aggressive tumors, Glioblastoma Multiforme has a mortality rate around 95% and survival’s average of 15 months, even though all treatment available. Temozolomide (TMZ) is the chemotherapeutic drug so far tested and approved with the highest response in this tumor sub-type and must be associated to other treatments to achieve better results. Thus, the purpose of this work was to evaluate the performance of this therapeutic modality with gold nanoparticles (AuNPs) and also combined with radiotherapy. TMZ hydrolysis was characterized at different pH and the chemical changes on molecular structure was determined via Fourier Transform Infrared Spectroscopy (FT-IR). The treatment performance was verified in vitro test using TMZ, TMZ plus AuNPs and associated with radiotherapy. The TMZ concentrations were varied from 0 (control group) to 1000µM, combined with AuNPs from 0 (control group) to10¹⁰ nanoparticles per well. The results showed the drug is stable at pH values between 2 to 4, but for pH values close to the physiological or basic medium, degradation is accentuated reaching a rate of 16 %/hour. The changes on molecular structure of TMZ can be observed through the FT-IR spectra, where the release of oxygen in the structure has influence on C=O group. The results of in vitro experiments showed that the highest poor results in the absence of ionizing irradiation. However, for experiments with TMZ and nanoparticles associated to radiotherapy, the performance of the treatment increased. In summary, the AuNPs showed important results under irradiation, revealing the same level of cytotoxicity for the highest TMZ concentration without irradiation. Also, the synergic effect between AuNPs and TMZ was observed under irradiation condition.