RESUMEN
Prolonged usage of traditional nanomaterials in the biological field has posed several short- and long-term toxicity issues. Over the past few years, smart nanomaterials (SNs) with controlled physical, chemical, and biological features have been synthesized in an effort to allay these challenges. The current study seeks to develop theranostic SNs based on iron oxide to enable simultaneous magnetic hyperthermia and magnetic resonance imaging (MRI), for chronic liver damage like liver fibrosis which is a major risk factor for hepatocellular carcinoma. To accomplish this, superparamagnetic iron oxide nanoparticles (SPIONs) were prepared, coated with a biocompatible and naturally occurring polysaccharide, alginate. The resultant material, ASPIONs were evaluated in terms of physicochemical, magnetic and biological properties. A hydrodynamic diameter of 40 nm and a transverse proton relaxation rate of 117.84 mM-1 s-1 pronounces the use of ASPIONs as an efficient MRI contrast agent. In the presence of alternating current of 300 A, ASPIONs could elevate the temperature to 45 °C or more, with the possibility of hyperthermia based therapeutic approach. Magnetic therapeutic and imaging potential of ASPIONs were further evaluated respectively in vitro and in vivo in HepG2 carcinoma cells and animal models of liver fibrosis, respectively. Finally, to introduce dual imaging capability along with magnetic properties, ASPIONs were conjugated with near infrared (NIR) dye Atto 700 and evaluated its optical imaging efficiency in animal model of liver fibrosis. Histological analysis further confirmed the liver targeting efficacy of the developed SNs for Magnetic theranostics and optical imaging as well as proved its short-term safety, in vivo.
Asunto(s)
Carcinoma Hepatocelular , Hipertermia Inducida , Neoplasias Hepáticas , Nanopartículas de Magnetita , Animales , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/terapia , Línea Celular Tumoral , Hipertermia Inducida/métodos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/terapia , Imagen por Resonancia Magnética/métodos , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/terapia , Hipertermia , Nanopartículas de Magnetita/químicaRESUMEN
Hybrid nanoparticles are innovative invention of last decade designed to overcome limitations of single-component nanoparticles by introducing multiple functionalities through combining two or more different nanoparticles. In this study, we are reporting development of magneto-fluorescent hybrid nanoparticles by combining iron oxide and carbon nanoparticles to enablein vivofluorescence imaging which also has all the required characteristic properties to use as Magnetic Resonance Imaging (MRI) contrast agent. In order to achieve dual-functional imaging, alginate and pullulan coated super paramagnetic iron oxide nanoparticles (ASPION and PSPION) and Carbon dots (Cdts) were synthesised separately. ASPIONs and PSPIONs were further chemically conjugated with Cdts and developed dual-functional nanohybrid particles ASPION-Cdts and PSPION-Cdts. Subsequently, evaluation of the materials for its size, functionalisation efficiency, fluorescence and magnetic properties, biocompatibility and cellular uptake efficiency has been carried out. Fluorescence imaging of liver fibrosis was performedin vivoin rodent model of liver fibrosis using the two nanohybrids, which is further confirmed by high fluorescence signal from the harvested liver.
Asunto(s)
Carbono , Nanopartículas , Humanos , Carbono/química , Compuestos Férricos/química , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/diagnóstico por imagen , Nanopartículas/química , Medios de Contraste/químicaRESUMEN
Early diagnosis and therapy of liver fibrosis is of utmost importance, especially considering the increased incidence of alcoholic and non-alcoholic liver syndromes. In this work, a systematic study is reported to develop a dual function and biocompatible nanoprobe for liver specific diagnostic and therapeutic applications. A polysaccharide polymer, pullulan stabilized iron oxide nanoparticle (P-SPIONs) enabled high liver specificity via asialogycoprotein receptor mediation. Longitudinal and transverse magnetic relaxation rates of 2.15 and 146.91 mM-1 s-1 respectively and a size of 12 nm, confirmed the T2 weighted magnetic resonance imaging (MRI) efficacy of P-SPIONs. A current of 400A on 5 mg/ml of P-SPIONs raised the temperature above 50 °C, to facilitate effective hyperthermia. Finally, a NIR dye conjugation facilitated targeted dual imaging in liver fibrosis models, in vivo, with favourable histopathological results and recommends its use in early stage diagnosis using MRI and optical imaging, and subsequent therapy using hyperthermia.
Asunto(s)
Receptor de Asialoglicoproteína/metabolismo , Biomarcadores , Glucanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/metabolismo , Imagen por Resonancia Magnética/métodos , Nanopartículas de Magnetita , Imagen Óptica/métodos , Animales , Materiales Biocompatibles , Línea Celular Tumoral , Supervivencia Celular , Fenómenos Químicos , Técnicas de Química Sintética , Compuestos Férricos/química , Glucanos/química , Cirrosis Hepática/etiología , Cirrosis Hepática/terapia , Nanopartículas de Magnetita/química , Masculino , Sondas Moleculares/síntesis química , Sondas Moleculares/química , Terapia Molecular Dirigida/métodos , Ratas , Especies Reactivas de OxígenoRESUMEN
Superparamagnetic iron oxide nanoparticles are widely used for the magnetic resonance imaging (MRI) applications. The surface characteristics, magnetic properties, size and targeting efficiency of the material are crucial factors for using the same as contrast agents. We report a simple synthesis method of citrate coated iron oxide nanoparticles and its systematic characterization. The developed system is highly water dispersible with an average particle size of 12 nm. The particles in water are monodisperse and are found to be stable over long periods. The efficiency of the material to de-phase water proton has been studied for various concentrations of iron using longitudinal (T1) and transverse (T2) weighted MRI. The coating thickness of the nanoparticle was optimized so that they exhibited a high transverse to longitudinal relaxivity (r2/r1) ratio of 37.92. A clear dose-dependent contrast enhancement was observed in T2 weighted in vivo MR imaging of liver fibrosis model in rodents. The labelling efficacy of the particle and the intracellular magnetic relaxivity were also investigated and presented. The particles were also tested for blood and cellular compatibility studies. Development of fibrosis and presence of iron in the liver was confirmed by histopathological analysis. From this study, we conclude that the citrate coated ultra small superparamagnetic iron oxide nanoparticles (C-USPION) with optimized parameters like particle size and magnetic property are capable of producing good MR contrast in imaging of liver diseases.
Asunto(s)
Citratos , Compuestos Férricos , Cirrosis Hepática/diagnóstico , Imagen por Resonancia Magnética , Nanopartículas , Animales , Comunicación Celular , Línea Celular Tumoral , Modelos Animales de Enfermedad , Humanos , Cirrosis Hepática/patología , Masculino , Nanopartículas/ultraestructura , Tamaño de la Partícula , Agregación Plaquetaria , Ratas Wistar , Reproducibilidad de los Resultados , Espectroscopía Infrarroja por Transformada de Fourier , Termogravimetría , Difracción de Rayos XRESUMEN
The field of medical imaging has recently seen rapid advances in the development of novel agents for enhancing image contrast. In particular, superparamagnetic iron oxide nanoparticles (SPIONs) with a variety of surface properties have been tried as effective contrast agents for magnetic resonance imaging, but with major side effects. In this study, the surface chemistry of SPIONs of size 12 nm was modified with high molecular weight dextran to yield particles of size 50 nm, without compromising the magnetic properties. A systematic characterization of the material for its size, coating efficiency, magnetic properties and biocompatibility has been carried out. The magnetic relaxivity as evaluated on a 1.5 T clinical magnet showed r2/r1 ratio of 56.28 which is higher than that reported for any other dextran stabilized ironoxide nanoparticles. Liver uptake and magnetic resonance imaging potential of dextran stabilized SPIONs (D-SPIONs) has been evaluated on liver fibrosis induced animal model, which is further supported by histopathology results.