RESUMO
Previously, we reported the preparation and preclinical studies of 99mTc-labeled gold nanoparticles-mannose (99mTc-AuNP-mannose) with potential for sentinel lymph node (SLN) detection by using nuclear medicine procedures. This study aimed to evaluate the biokinetics and hybrid (2D/3D) dosimetry of 99mTc-AuNP-mannose in five patients with breast cancer under a sentinel lymph node detection protocol. Anterior and posterior whole-body planar images (2D, at 0.5, 2, 6, and 24 h) and single-photon emission computed tomography (3D at 6.5 h)/computed tomography (SPECT/CT) images were acquired after 99mTc-AuNP-mannose administration (37 MBq). Through a hybrid quantification method, activity in tissues of interest at the different acquisition times was determined and integrated over time to obtain the total nuclear transformations (N), as well as the mean residence time, in each tissue. N values and the OLINDA code were used for estimating the internal radiation absorbed doses. Results demonstrated that 99mTc-AuNP-mannose successfully accumulates and remains up to 24 h in the sentinel lymph node without detectable migration to other lymph nodes and no side effects on patients. Negligible absorption of the radiolabeled nanoparticles into the circulatory system was observed, from which the radio-nanosystem is rapidly eliminated by kidneys. Hybrid (2D/3D) dosimetry evaluations showed equivalent doses to SLN, breast, and kidneys of 172.34, 5.32, and 0.08 mSv/37 MBq, respectively, with an effective dose of 2.05E - 03 mSv/MBq. The mean effective residence time in SLN was 0.92 h. This preliminary study indicates that the use of 99mTc-AuNP-mannose for successful SLN detection in patients is safe, producing an effective dose at the level recommended for diagnostic studies (<10 mSv).
Assuntos
Neoplasias da Mama/diagnóstico por imagem , Ouro/química , Nanopartículas Metálicas/química , Radiometria , Linfonodo Sentinela/diagnóstico por imagem , Adulto , Idoso , Feminino , Ouro/farmacocinética , Humanos , Manose/farmacocinética , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/farmacocinética , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Tecnécio/farmacocinéticaRESUMO
This study aimed to elucidate the anti-inflammatory, anti-oxidant and antifibrotic effects of gold nanoparticles (GNPs) in rats subjected to liver injury with ethanol and Methamphetamine (METH). The liver injury was induced by gavage administrations of 30% alcoholic solution (7â¯g/kg) once a day during 28â¯days, followed by METH (10â¯mg/kg) on the 20th and 28thâ¯days of treatment. GNPs treatment (724.96⯵g/kg) during the ethanol and METH exposure was associated with reduced steatosis, hepatic cord degeneration, fibrosis and necrosis. Furthermore, there was a reduction in biochemical markers of liver damage and oxidative stress, and pro-inflammatory cytokines IL-1ß and TNF-α, compared to ethanolâ¯+â¯METH group alone. A decrease of FGF, SOD-1 and GPx-1 expression was also observed. GNPs down-regulated the activity of Kupffer cells and hepatic stellate cells affecting the profile of their pro-inflammatory cytokines, oxidative stress and fibrosis through modulation of signaling pathways AKT/PI3K and MAPK in ethanolâ¯+â¯METH-induced liver injury in a rat model.
Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Ouro/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Nanopartículas Metálicas/uso terapêutico , Animais , Anti-Inflamatórios/farmacocinética , Antioxidantes/farmacocinética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Citocinas/metabolismo , Etanol , Fatores de Crescimento de Fibroblastos/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Ouro/farmacocinética , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Malondialdeído/metabolismo , Metanfetamina , Camundongos , NF-kappa B/genética , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Células RAW 264.7 , Ratos , Ratos Wistar , Superóxido Dismutase-1/metabolismo , Glutationa Peroxidase GPX1RESUMO
An exciting and emerging field in nanomedicine involves the use of gold nanoparticles (AuNPs) in the preclinical development of new strategies for the treatment and diagnosis of brain-related diseases such as neurodegeneration and cerebral tumors. The treatment of many brain-related disorders with AuNPs, which possess useful physical properties, is limited by the blood-brain barrier (BBB). The BBB highly regulates the substances that can permeate into the brain. Peptides and proteins may represent promising tools to improve the delivery of AuNPs to the central nervous system (CNS). In this review, we summarize the potential applications of AuNPs to CNS disorders, discuss different strategies based on the use of peptides or proteins to improve the delivery of AuNPs to the brain, and examine the intranasal administration route, which bypasses the BBB. We also analyze the potential neurotoxicity of AuNPs and the perspectives and new challenges concerning the use of peptides and proteins to enhance the delivery of AuNPs to the brain. The majority of the work described in this review is in a preclinical stage of experimentation, or in select cases, in clinical trials in humans. We note that the use of AuNPs still requires substantial study before being translated into human applications. However, for further clinical research, the issues related to the potential use of AuNPs must be analyzed.
Assuntos
Encéfalo/metabolismo , Portadores de Fármacos , Ouro , Nanopartículas Metálicas , Nanomedicina/métodos , Peptídeos , Encefalopatias , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/uso terapêutico , Portadores de Fármacos/toxicidade , Ouro/química , Ouro/farmacocinética , Ouro/uso terapêutico , Ouro/toxicidade , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Nanopartículas Metálicas/toxicidade , Peptídeos/química , Peptídeos/farmacocinética , Peptídeos/uso terapêutico , Peptídeos/toxicidade , Proteínas/química , Proteínas/farmacocinética , Proteínas/uso terapêutico , Proteínas/toxicidadeRESUMO
Integrin α(V)ß(3) plays a critical role in tumor angiogenesis and metastasis. Suitably radiolabeled cyclic RGD peptides can be used for noninvasive imaging of α(V)ß(3) expression. The aim of this research was to prepare a multimeric system of technetium-99m-labeled gold nanoparticles conjugated to c[RGDfK(C)] and to evaluate its biological behavior as a potential radiopharmaceutical for molecular imaging of tumor angiogenesis. Hydrazinonicotinamide-GGC (HYNIC-GGC) and c[RGDfK(C)] peptides were synthesized and conjugated to gold nanoparticles (AuNP, 20 nm) by means of spontaneous reaction of the thiol groups of cysteine. The nanoconjugate was characterized by TEM, FT-IR, UV-vis, XPS, and Raman spectroscopy. To obtain (99m)Tc-HYNIC-GGC-AuNP-c[RGDfK(C)] ((99m)Tc-AuNP-RGD), the (99m)Tc-HYNIC-GGC radiopeptide was first prepared and added to 1.5 mL of AuNP solution (1 nM) followed by c[RGDfK(C)] (10 µL, 50 µM) at 18 °C with stirring for 15 min. Radiochemical purity (RP) was determined by size-exclusion HPLC and ITLC-SG analyses. In vitro binding studies were carried out in α(V)ß(3) receptor-positive C6 glioma cancer cells. Biodistribution studies were accomplished in athymic mice with C6-induced tumors with blocked and nonblocked receptors, and images were obtained using a micro-SPECT/CT. TEM and spectroscopy techniques demonstrated that AuNPs were functionalized with peptides. RP was 96 ± 2% without postlabeling purification. (99m)Tc-AuNP-RGD showed specific recognition for α(V)ß(3) integrins expressed in C6 cells, and 3 h after i.p. administration in mice, the tumor uptake was 8.18 ± 0.57% ID/g. Micro-SPECT/CT images showed evident tumor uptake. (99m)Tc-AuNP-RGD demonstrates properties suitable for use as a target-specific agent for molecular imaging of tumor α(V)ß(3) expression.
Assuntos
Glioma/metabolismo , Ouro , Integrina alfaVbeta3/análise , Nanopartículas Metálicas , Imagem Molecular , Compostos de Organotecnécio , Peptídeos Cíclicos , Animais , Linhagem Celular Tumoral , Feminino , Glioma/patologia , Ouro/química , Ouro/farmacocinética , Humanos , Integrina alfaVbeta3/biossíntese , Marcação por Isótopo , Nanopartículas Metálicas/química , Camundongos , Camundongos Nus , Estrutura Molecular , Compostos de Organotecnécio/química , Compostos de Organotecnécio/farmacocinética , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacocinética , Distribuição TecidualRESUMO
In order to evaluate the interactions between Au/Cu atoms and clean Si(111) surface, we used synchrotron radiation grazing incidence X-ray fluorescence analysis and theoretical calculations. Optimized geometries and energies on different adsorption sites indicate that the binding energies at different adsorption sites are high, suggesting a strong interaction between metal atom and silicon surface. The Au atom showed higher interaction than Cu atom. The theoretical and experimental data showed good agreement.
Assuntos
Cobre/farmacocinética , Ouro/farmacocinética , Modelos Teóricos , Silício/metabolismo , Síncrotrons , Absorção , Cobre/química , Ouro/química , Modelos Biológicos , Modelos Moleculares , Estrutura Molecular , Silício/química , Espectrometria por Raios X/instrumentação , Espectrometria por Raios X/métodos , Propriedades de SuperfícieRESUMO
Se evaluó el tratamiento de la artritis reumatoide con compuestos de oro, en la Unidad de Inmunoreumatología de la UPCH, Hospital Cayetano Heredia, periodo Enero 1973 - Marzo 1989. Se agrupó pacientes según el compuesto usado: oro inyectable (OI) y oro oral (OO). El grupo OI tuvo n igual 41 y edad promedio 39.9 años; el grupo OO tuvo n igual 20 y edad promedio 35 años. Las características clínicas no fueron estadísticamente diferentes, salvo edad y tiempo de seguimiento, menores para el grupo OO. El grupo OI alcanzó mejoria clínica significativa en 91.6 por ciento: 43 por ciento remisión completa, 40 por ciento buena respuesta, 8.6 por ciento respuesta aceptable. El grupo OO alcanzó mejoría clínica significativa en 60 por ciento: 6.7 por ciento remisión completa, 33.3 por ciento buena respuesta, 20 por ciento respuesta aceptable. La probalidad de permanencia en terapia en OI fue 71 por ciento a los 6 meses, 59 por ciento a los 12 m, 37 por ciento a los 24 m., y en OO fue 64 por ciento a los 6 meses y 32 por ciento a los 12m. La probalidad de permanencia corregida en terapia en OI fue 72 por ciento al año, 56 por ciento a los dos años; y en OO fue de 52 por ciento al año; las permanencias corregidas no fueron estadísticamente diferentes al primer año. Con OI hubo 83 por ciento de efectos adversos; con OO 45 por ciento; con OI fueron de mayor severidad y con mayor número de suspensiones. Con OI hubo 39 por ciento de retiros injustificados, con OO 45 por ciento. Las causas de suspensión no justificadas fueron de orden social, económico, educativo y médico