Near infrared-emitting multimodal nanosystem for in vitro magnetic hyperthermia of hepatocellular carcinoma and dual imaging of in vivo liver fibrosis.

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.

Fluorescent carbon dots tailored iron oxide nano hybrid system forin vivooptical imaging of liver fibrosis.

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.

Asialoglycoprotein receptor targeted optical and magnetic resonance imaging and therapy of liver fibrosis using pullulan stabilized multi-functional iron oxide nanoprobe.

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.

Biosafety of citrate coated zerovalent iron nanoparticles for Magnetic Resonance Angiography.

Though nanoparticles are being used for several biomedical applications, the safety of the same is still a concern. It is very routine procedure to check the preliminary safety aspects of the particles intended for in vivo applications. The major tests include how the material reacts to a normal cell, how it behaves with the blood cells and also whether any lysis take place in the presence of these materials. Here we present these test data of two novel nanomaterials designed for its use as contrast agent for magnetic resonance imaging and a multimodal contrast agent for targeted liver imaging. On proving the biosafety, the materials were tested for Magnetic Resonance Angiography using normal rats as model. The data of the same were clear identification of the prominent vascular structures and is included as the colour coded MRI image. Lateral and oblique view data are also presented for visualizing other major blood vessels.

Multifunctional hybrid nanoconstruct of zerovalent iron and carbon dots for magnetic resonance angiography and optical imaging: An In vivo study.

In magnetic resonance imaging (MRI), gadolinium (Gd) complexes are very often used as contrast agents to enhance the signal from soft tissue deformities and vascular anomalies, to improve the accuracy of diagnosis. The safety concern of using Gd complexes in renally compromised patients pose limitations on its application. To overcome this scenario, we introduce a nontoxic zerovalent iron based nanoparticle as a novel contrast agent for MR angiography and a hybrid version of the same to serve as a dual function contrast agent for targeted liver imaging. The synthesized zerovalent iron (ZVI) nanoparticles after citrate stabilization (C@ZVI) had an average size of 10 nm and exhibited paramagnetic property which is a prerequisite for a positive MRI contrast agent. The longitudinal magnetic relaxivity, r1 of C@ZVI was 4.93 mM-1s-1 which is much higher than that of clinically used Gd based agent, gadoterate meglumine (3.6 mM-1s-1). For multimodal imaging of the liver, initially the ZVI nanoparticle was tailored with a highly liver specific polysaccharide pullulan, and later with fluorescent carbon dots (Cdts) facilitating both optical and MR imaging. The magnetic relaxivity was retained in P@ZVI-Cdts for T1 contrast imaging with an r1 value of 3.48 mM-1s-1. The in vivo MR angiogram using C@ZVI and the liver targeted MRI and optical imaging using P@ZVI-Cdts were successfully demonstrated proving their potential as MRA contrast agent and a liver specific multimodal imaging agent.

Citrate coated iron oxide nanoparticles with enhanced relaxivity for in vivo magnetic resonance imaging of liver fibrosis.

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.

Synthesis and characterization of dextran stabilized superparamagnetic iron oxide nanoparticles for in vivo MR imaging of liver fibrosis.

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.

Fluorescence spectroscopy as a highly potential single-entity tool to identify chromophores and fluorophores: study on neoplastic human brain lesions.

Fluorescence and diffuse reflectance spectroscopy are powerful tools to differentiate normal and malignant tissue based on the emissions from endogenous fluorophores and diffuse reflection of absorbers such as hemoglobin. However, separate analytical methods are used for the identification of fluorophores and hemoglobin. The estimation of fluorophores and hemoglobin simultaneously using a single technique of autofluorescence spectroscopy is reported, and its diagnostic potential on clinical tissue samples is potentially exploited. Surgically removed brain tissues from patients that are later identified pathologically as astrocytoma, glioma, meningioma, and schwannoma are studied. The emissions from prominent fluorophores collagen, flavin adenine dinucleotide, phospholipids, and porphyrin are analyzed at 320 and 410 nm excitations. The hemoglobin concentration is also calculated from the ratio of fluorescence emissions at 500 and 570 nm. A better classification of normal and tumor tissues is yielded for 410 nm excitation compared to 320 nm when diagnostic algorithm based on linear discriminant analysis is used. The potential of fluorescence spectroscopy as a single entity to evaluate the prominent fluorophores as well as the hemoglobin concentration within normal and tumor brain tissues is emphasized.

Optimum wavelength for the differentiation of brain tumor tissue using autofluorescence spectroscopy.

OBJECTIVE: The role of autofluorescence spectroscopy in the detection and staging of benign and malignant brain tumors is being investigated in this study, with an additional aim of determining an optimum excitation wavelength for the spectroscopic identification of brain tumors. MATERIALS AND METHODS: The present study involves in-vitro autofluorescence monitoring of different human brain tumor samples to assess their spectroscopic properties. The autofluorescence measurement at four different excitation wavelengths 320, 370, 410, and 470 nm, were carried out for five different brain tumor types: glioma, astrocytoma, meningioma, pituitary adenoma, and schwannoma. RESULTS: The fluorescence spectra of tumor tissues showed significant differences, both in intensity and in spectral profile, from those of adjacent normal brain tissues at all four excitation wavelengths. The data were then subjected to multivariate statistical analysis and the sensitivities and specificities were calculated for each group. Of the four excitation wavelengths being considered, 470 nm appeared to be the optimal wavelength for detecting tissue fluorescence of brain tumor tissues. CONCLUSIONS: In conclusion, the spectroscopic luminescence measurements carried out in this study revealed significant differences between tumor tissue and adjacent normal tissue of human brains for all the tumor types tested, except for pituitary adenoma. From the results of this study we conclude that excitation wavelengths ranging from 410-470 nm are most suitable for the detection of brain tumor tissue. Moreover, in this particular study, only excitation at 470 nm indicated that samples we considered to be normal tissue were not normal, and that these were indeed pituitary adenoma tissues. This distinction was not clear at other excitation wavelengths.