RESUMEN
This study aims to explore the ability of magnetic resonance imaging (MRI) in mucin 1 (MUC1) modified superparamagnetic iron oxide nanoparticle (SPION) targeting human pancreatic cancer (PC). The MUC1 target-directed probe was prepared through MUC1 conjugated to SPION using the chemical method to assess its physiochemical characteristics, including hydration diameter, surface charge, and magnetic resonance signal. The cytotoxicity of MUC1-USPION was verified by MTS assay. BxPC-3 was cultured with MUC1-USPION and SPION in different concentrations. The combined condition of the targeted probes and cells were observed through Prussian blue staining. The nude mice model of pancreatic cancer was established to investigate the application of the probe. MRI was performed to determine the intensity of the signal of the transplanted tumor, while immunohistochemistry and Western blot analysis were performed to detect the expression of MUC1 after taking the transplanted tumor specimen. The particle size of the prepared molecular probe was 63.5 ± 3.2 nm, and the surface charge was 10.2 mV. Furthermore, the probe solution could significantly reduce the MRI at T2 , and the magnetic resonance transverse relaxation rate (ΔR2 ) has a linear relationship with the concentration of iron in the solution. The cell viability of MUC1-USPION in different concentrations revealed no statistical difference, according to the MTS assay. In vitro, the MRI demonstrated decreased T2WI signal intensity in both groups, especially the targeting group. In vivo, MUC1 could selectively accumulate in the nude mice model, and significantly reduce the T2 signal strength. In subsequent experiments, the expression of MUC1 was high in pancreatic cancer tissues, but low in normal pancreatic tissues, as determined by immunohistochemistry and Western blot analysis. The prepared samples can be combined with pancreatic cancer tissue specificity by in vivo imaging, providing reliable early in vivo imaging data for disease diagnosis.
Asunto(s)
Aptámeros de Nucleótidos/química , Imagen por Resonancia Magnética/métodos , Nanopartículas de Magnetita/química , Mucina-1/química , Neoplasias Pancreáticas/metabolismo , Animales , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/metabolismo , Aptámeros de Nucleótidos/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Medios de Contraste/administración & dosificación , Medios de Contraste/química , Medios de Contraste/metabolismo , Humanos , Inmunohistoquímica , Nanopartículas de Magnetita/administración & dosificación , Ratones Desnudos , Mucina-1/genética , Mucina-1/metabolismo , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/terapia , Tamaño de la Partícula , Ensayos Antitumor por Modelo de Xenoinjerto/métodosRESUMEN
Nosocomial infections caused by carbapenemase-producing Enterobacteriaceae have emerged as an important challenge worldwide and represent a great limitation for antimicrobial therapy. Detection of carbapenemase in Enterobacteriaceae species also remains challenging. Although the modified Hodge test is recommended, it lacks specificity and is unable to distinguish between carbapenemase types. Here, we demonstrated a screening strategy for the phenotypic detection of carbapenemases among Enterobacteriaceae isolates in the clinical laboratory by using ethylenediaminetetraacetic acid and phenylboronic acid. This strategy displayed an overall 100% sensitivity and 98.6% specificity for carbapenemase detection in Enterobacteriaceae, which was superior to that of the modified Hodge test (98.0% sensitivity and 84.3% specificity), and it also discriminated the carbapenemase phenotypes of KPC-2, VIM-1, and OXA-48.