Dendrimer functionalized magnetic nanoparticles as a promising platform for localized hyperthermia and magnetic resonance imaging diagnosis

Magnetic iron oxide nanoparticles are a well-explored class of nanomaterials known for their high magnetization and biocompatibility. They have been used in various biomedical applications such as drug delivery, biosensors, hyperthermia, and magnetic resonance imaging (MRI) contrast agent. It is necessary to surface modify the nanoparticles with a biocompatible moiety to prevent their agglomeration and enable them to target to the defined area. Dendrimers have attracted considerable attention due to their small size, monodispersed, well-defined globular shape, and a relative ease incorporation of targeting ligands. In this study, superparamagnetic iron oxide nanoparticles were synthesized via a coprecipitation method. The magnetic nanoparticles (MNPs) had been modified with (3-aminopropyl) triethoxysilane, and then polyamidoamine functionalized MNPs had been synthesized cycling. Various characterization techniques had been used to reveal the morphology, size, and structure of the nanoparticles such as scanning electron microscopy, transmission electron microscope, X-ray diffraction analysis, and vibrating sample magnetometer, Fourier-transform infrared spectroscopy and zeta potential measurements. In addition, the cytotoxicity property of G3–dendrimer functionalized MNPs were evaluated using 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide assay which confirmed the biocompatibility of the nanocomposites. Dendrimer functionalized MNPs are able to act as contrast agents for MRI and magnetic fluid hyperthermia mediators. A superior heat generation was achieved for the given concentration according to the hyperthermia results. MRI results show that the synthesized nanocomposites are a favorable option for MRI contrast agent. We believe that these dendrimer functionalized MNPs have the potential of integrating therapeutic and diagnostic functions in a single carrier.     

Cell labeling with magnetic nanoparticles: Opportunity for magnetic cell imaging and cell manipulation

This tutorial describes a method of controlled cell labeling with citrate-coated ultra small superparamagnetic iron oxide nanoparticles. This method may provide basically all kinds of cells with sufficient magnetization to allow cell detection by high-resolution magnetic resonance imaging (MRI) and to enable potential magnetic manipulation. In order to efficiently exploit labeled cells, quantify the magnetic load and deliver or follow-up magnetic cells, we herein describe the main requirements that should be applied during the labeling procedure. Moreover we present some recommendations for cell detection and quantification by MRI and detail magnetic guiding on some real-case studies in vitro and in vivo.     

Improvement of MRI probes to allow efficient detection of gene expression

Recently, it has been demonstrated that magnetic resonance imaging (MRI) utilizing monocrystalline iron oxide nanoparticles (MIONs) targeted to an engineered transferrin receptor enables imaging of gene expression. However, the relatively high doses of iron oxides used indicated the need for improved MR imaging probes to monitor changes in gene expression in vivo. Using alternative conjugation chemistries to link targeting ligands and iron oxide nanoparticles, we present the development and characterization as well as improved receptor binding and MRI detection of a novel imaging probe. Iron oxide nanoparticles with a cross-linked dextran coat were conjugated to transferrin (Tf) through the linker molecule N-succinimidyl 3-(2-pyridyldithio)propionate (SPDP) to yield Tf-S-S-CLIO. The characteristics of this conjugate were evaluated in comparison to Tf-MION and Tf-CLIO generated by oxidative activation of the dextran-coat with subsequent reduction of Schiff's base. SPDP conjugation allowed approximately a 4-fold increase in the number of Tf molecules attached per iron oxide nanoparticle and resulted in a more than 10-fold improvement of binding and uptake by cells. This translated into an imaging probe that was 16 times better for imaging gene expression in a cellular MRI assay. This novel probe for MRI may substantially increase the sensitivity for the detection of endogenous or genetically induced transferrin receptor expression in small numbers of cells and may significantly reduce the imaging dose from over 100 mg/kg to doses of iron oxides that are currently used in clinical imaging.     

In-Vivo Imaging of Cell Migration Using Contrast Enhanced MRI and SVM Based Post-Processing

The migration of cells within a living organism can be observed with magnetic resonance imaging (MRI) in combination with iron oxide nanoparticles as an intracellular contrast agent. This method, however, suffers from low sensitivity and specificty. Here, we developed a quantitative non-invasive in-vivo cell localization method using contrast enhanced multiparametric MRI and support vector machines (SVM) based post-processing. Imaging phantoms consisting of agarose with compartments containing different concentrations of cancer cells labeled with iron oxide nanoparticles were used to train and evaluate the SVM for cell localization. From the magnitude and phase data acquired with a series of T2*-weighted gradient-echo scans at different echo-times, we extracted features that are characteristic for the presence of superparamagnetic nanoparticles, in particular hyper- and hypointensities, relaxation rates, short-range phase perturbations, and perturbation dynamics. High detection quality was achieved by SVM analysis of the multiparametric feature-space. The in-vivo applicability was validated in animal studies. The SVM detected the presence of iron oxide nanoparticles in the imaging phantoms with high specificity and sensitivity with a detection limit of 30 labeled cells per mm³, corresponding to 19 μM of iron oxide. As proof-of-concept, we applied the method to follow the migration of labeled cancer cells injected in rats. The combination of iron oxide labeled cells, multiparametric MRI and a SVM based post processing provides high spatial resolution, specificity, and sensitivity, and is therefore suitable for non-invasive in-vivo cell detection and cell migration studies over prolonged time periods.     

Iron Oxide Nanoparticle-Micelles (ION-Micelles) for Sensitive (Molecular) Magnetic Particle Imaging and Magnetic Resonance Imaging

Background

Iron oxide nanoparticles (IONs) are a promising nanoplatform for contrast-enhanced MRI. Recently, magnetic particle imaging (MPI) was introduced as a new imaging modality, which is able to directly visualize magnetic particles and could serve as a more sensitive and quantitative alternative to MRI. However, MPI requires magnetic particles with specific magnetic properties for optimal use. Current commercially available iron oxide formulations perform suboptimal in MPI, which is triggering research into optimized synthesis strategies. Most synthesis procedures aim at size control of iron oxide nanoparticles rather than control over the magnetic properties. In this study, we report on the synthesis, characterization and application of a novel ION platform for sensitive MPI and MRI.

Methods and Results

IONs were synthesized using a thermal-decomposition method and subsequently phase-transferred by encapsulation into lipidic micelles (ION-Micelles). Next, the material and magnetic properties of the ION-Micelles were analyzed. Most notably, vibrating sample magnetometry measurements showed that the effective magnetic core size of the IONs is 16 nm. In addition, magnetic particle spectrometry (MPS) measurements were performed. MPS is essentially zero-dimensional MPI and therefore allows to probe the potential of iron oxide formulations for MPI. ION-Micelles induced up to 200 times higher signal in MPS measurements than commercially available iron oxide formulations (Endorem, Resovist and Sinerem) and thus likely allow for significantly more sensitive MPI. In addition, the potential of the ION-Micelle platform for molecular MPI and MRI was showcased by MPS and MRI measurements of fibrin-binding peptide functionalized ION-Micelles (FibPep-ION-Micelles) bound to blood clots.

Conclusions

The presented data underlines the potential of the ION-Micelle nanoplatform for sensitive (molecular) MPI and warrants further investigation of the FibPep-ION-Micelle platform for in vivo, non-invasive imaging of fibrin in preclinical disease models of thrombus-related pathologies and atherosclerosis.     

Formulation of novel lipid-coated magnetic nanoparticles as the probe for in vivo imaging

Background  

Application of superparamagnetic iron oxide nanoparticles (SPIOs) as the contrast agent has improved the quality of magnetic resonance (MR) imaging. Low efficiency of loading the commercially available iron oxide nanoparticles into cells and the cytotoxicity of previously formulated complexes limit their usage as the image probe. Here, we formulated new cationic lipid nanoparticles containing SPIOs feasible for in vivo imaging.     

Superparamagnetic Iron Oxide Nanoparticles Function as a Long-Term,Multi-Modal Imaging Label for Non-Invasive Tracking of Implanted Progenitor Cells

The purpose of this study was to determine the ability of superparamagnetic iron oxide (SPIO) nanoparticles to function as a long-term tracking label for multi-modal imaging of implanted engineered tissues containing muscle-derived progenitor cells using magnetic resonance imaging (MRI) and X-ray micro-computed tomography (μCT). SPIO-labeled primary myoblasts were embedded in fibrin sealant and imaged to obtain intensity data by MRI or radio-opacity information by μCT. Each imaging modality displayed a detection gradient that matched increasing SPIO concentrations. Labeled cells were then incorporated in fibrin sealant, injected into the atrioventricular groove of rat hearts, and imaged in vivo and ex vivo for up to 1 year. Transplanted cells were identified in intact animals and isolated hearts using both imaging modalities. MRI was better able to detect minuscule amounts of SPIO nanoparticles, while μCT more precisely identified the location of heavily-labeled cells. Histological analyses confirmed that iron oxide particles were confined to viable, skeletal muscle-derived cells in the implant at the expected location based on MRI and μCT. These analyses showed no evidence of phagocytosis of labeled cells by macrophages or release of nanoparticles from transplanted cells. In conclusion, we established that SPIO nanoparticles function as a sensitive and specific long-term label for MRI and μCT, respectively. Our findings will enable investigators interested in regenerative therapies to non-invasively and serially acquire complementary, high-resolution images of transplanted cells for one year using a single label.     

MRI detection of thrombin with aptamer functionalized superparamagnetic iron oxide nanoparticles

Design of smart MRI contrast agent based on superparamagnetic iron oxide nanoparticles and aptamers has been described for the detection of human alpha-thrombin protein. The contrast agent is based on the assembly of the aptamer functionalized nanoparticles in the presence of thrombin. A detectable change in MRI signal is observed with 25 nM thrombin in human serum. Changes were neither observed with control analytes, streptavidin, or bovine serum albumin, nor with inactive aptamer functionalized nanoparticles.     

New Strategies to Prolong the In Vivo Life Span of Iron-Based Contrast Agents for MRI

Superparamagnetic iron oxide (SPIO) and ultra small superparamagnetic iron oxide (USPIO) nanoparticles have been developed as magnetic resonance imaging (MRI) contrast agents. Iron oxide nanoparticles, that become superparamagnetic if the core particle diameter is ^~ 30nm or less, present R1 and R2 relaxivities which are much higher than those of conventional paramagnetic gadolinium chelates. Generally, these magnetic particles are coated with biocompatible polymers that prevent the agglomeration of the colloidal suspension and improve their blood distribution profile. In spite of their potential as MRI blood contrast agents, the biomedical application of iron oxide nanoparticles is still limited because of their intravascular half-life of only few hours; such nanoparticles are rapidly cleared from the bloodstream by macrophages of the reticulo-endothelial system (RES). To increase the life span of these MRI contrast agents in the bloodstream we proposed the encapsulation of SPIO nanoparticles in red blood cells (RBCs) through the transient opening of cell membrane pores. We have recently reported results obtained by applying our loading procedure to several SPIO nanoparticles with different chemical physical characteristics such as size and coating agent. In the current investigation we showed that the life span of iron-based contrast agents in the mice bloodstream was prolonged to 12 days after the intravenous injection of murine SPIO-loaded RBCs. Furthermore, we developed an animal model that implicates the pretreatment of animals with clodronate to induce a transient suppression of tissue macrophages, followed by the injection of human SPIO-loaded RBCs which make it possible to encapsulate nanoparticle concentrations (5.3-16.7mM Fe) higher than murine SPIO-loaded RBCs (1.4-3.55mM Fe). The data showed that, when human RBCs are used as more capable SPIO nanoparticle containers combined with a depletion of tissue macrophages, Fe concentration in animal blood is 2-3 times higher than iron concentration obtained by the use of murine SPIO-loaded RBCs.     

Magnetically controlled release of cisplatin from superparamagnetic starch nanoparticles

The present study involves a novel strategy for the preparation of superparamagnetic nanoparticles of crosslinked starch impregnated with homogeneously dispersed nanosized iron oxide. The nanoparticles were loaded with an anticancer drug ‘cisplatin’ and the drug release kinetics was investigated spectrophotometrically at physiological pH (7.4). The nanoparticles were characterized by Fourier transform infra red (FTIR) spectroscopy, transmission electron microscopy (TEM), X-ray diffraction and magnetization studies. The particle size of magnetic starch nanoparticles was found to lie in the range of 20-90 nm. The influence of factors like chemical composition of nanoparticles, pH and temperature of the release media and applied magnetic field was investigated on the release profiles of the drug. The prepared nanoparticles could provide a possible pathway for targeted and controlled delivery of anticancer drugs minimizing side effects and achieving higher efficacy.     

Development of SM5-1-conjugated ultrasmall superparamagnetic iron oxide nanoparticles for hepatoma detection

Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are maghemite or magnetite nanoparticles currently used as contrast agent in magnetic resonance imaging (MRI). In this study, a targeted contrast agent (SM-USPIO) was prepared by conjugating coprecipitated USPIO to a humanized SM5-1 antibody which can specifically react with human hepatocellular carcinoma (HCC) cells. The binding and internalization of SM-USPIO to the HCC cell line ch-hep-3 was confirmed by flow cytometry and confocal microscopy. Furthermore, SM-USPIO was demonstrated to be able to selectively accumulate in the tumor cells, resulting in a marked decrease of MRI T2-weighted signal intensity. Biodistribution studies demonstrated the efficient accumulation of SM-USPIO in the ch-hep-3 tumor in nude mice. The in vivo study in the ch-hep-3 tumor-bearing nude mice indicated that MRI using the SM-USPIO as contrast agent possessed good diagnostic ability, suggesting that SM-USPIO had the potential to be a promising targeted contrast agent for diagnosis of HCC.     

Magnetic characterization of superparamagnetic nanoparticles pulled through model membranes

Background

To quantitatively compare in-vitro and in vivo membrane transport studies of targeted delivery, one needs characterization of the magnetically-induced mobility of superparamagnetic iron oxide nanoparticles (SPION). Flux densities, gradients, and nanoparticle properties were measured in order to quantify the magnetic force on the SPION in both an artificial cochlear round window membrane (RWM) model and the guinea pig RWM.

Methods

Three-dimensional maps were created for flux density and magnetic gradient produced by a 24-well casing of 4.1 kilo-Gauss neodymium-iron-boron (NdFeB) disc magnets. The casing was used to pull SPION through a three-layer cell culture RWM model. Similar maps were created for a 4 inch (10.16 cm) cube 48 MGOe NdFeB magnet used to pull polymeric-nanoparticles through the RWM of anesthetized guinea pigs. Other parameters needed to compute magnetic force were nanoparticle and polymer properties, including average radius, density, magnetic susceptibility, and volume fraction of magnetite.

Results

A minimum force of 5.04 × 10^-16 N was determined to adequately pull nanoparticles through the in-vitro model. For the guinea pig RWM, the magnetic force on the polymeric nanoparticles was 9.69 × 10^-20 N. Electron microscopy confirmed the movement of the particles through both RWM models.

Conclusion

As prospective carriers of therapeutic substances, polymers containing superparamagnetic iron oxide nanoparticles were succesfully pulled through the live RWM. The force required to achieve in vivo transport was significantly lower than that required to pull nanoparticles through the in-vitro RWM model. Indeed very little force was required to accomplish measurable delivery of polymeric-SPION composite nanoparticles across the RWM, suggesting that therapeutic delivery to the inner ear by SPION is feasible.

     

In vivo molecular imaging using nanomaterials: General in vivo characteristics of nano-sized reagents and applications for cancer diagnosis (Review)

Abstract

Nanoparticles present a new collection of contrast agents for the field of in vivo molecular imaging. This review focuses on promising molecular imaging probes for optical and magnetic resonance imaging based on four representative nanomaterial(s) platforms: quantum dots, upconversion phosphors, superparamagnetic iron oxides, and dendrimer-based agents. Quantum dots are extremely efficient fluorescent nanoparticles with size-tunable emission properties, enabling high sensitivity and greater depth penetration. Their heavy metal composition and long retention in the body, however, pose concerns for clinical translational applications. Upconversion phosphors generate excellent signal-to-background contrast because they emit light with higher energy than the excitation photons and autofluorescence signals. For MRI, iron oxide particles also generate excellent signal and have been used in liver imaging and for cell tracking studies. As they are metabolized through endogenous iron salvage pathways, they have already been introduced as clinical contrast agents. Lastly, dendrimers, a ‘soft’ nanoparticle, can be used as a structural basis for the attachment of small molecule imaging agents and/or targeting groups. This array of nanoparticles should offer insights into the uses and potentials of nanoparticles for the molecular imaging.     

磁性氧化铁纳米颗粒及其磁共振成像应用

磁性氧化铁纳米颗粒在磁共振成像方面的应用,已经在全世界范围内得到了广泛的关注,相关研究也被各国科学家高度重视.目前,磁性氧化铁纳米颗粒正在从早期的基于被动识别的肝部磁共振造影,快速转向基于主动识别的磁共振分子影像应用.本文将围绕磁性氧化铁纳米颗粒的生物体内应用,着重介绍磁性纳米颗粒的制备及其在疾病诊断,尤其是在肿瘤早期...     

Magnetic resonance cell-tracking studies: spectrophotometry-based method for the quantification of cellular iron content after loading with superparamagnetic iron oxide nanoparticles

The purpose of this article is to present a user-friendly tool for quantifying the iron content of superparamagnetic labeled cells before cell tracking by magnetic resonance imaging (MRI). Iron quantification was evaluated by using Prussian blue staining and spectrophotometry. White blood cells were labeled with superparamagnetic iron oxide (SPIO) nanoparticles. Labeling was confirmed by light microscopy. Subsequently, the cells were embedded in a phantom and scanned on a 3 T magnetic resonance tomography (MRT) whole-body system. Mean peak wavelengths λ(peak) was determined at A(720 nm) (range 719-722 nm). Linearity was proven for the measuring range 0.5 to 10 μg Fe/mL (r = .9958; p = 2.2 × 10(-12)). The limit of detection was 0.01 μg Fe/mL (0.1785 mM), and the limit of quantification was 0.04 μg Fe/mL (0.714 mM). Accuracy was demonstrated by comparison with atomic absorption spectrometry. Precision and robustness were also proven. On T(2)-weighted images, signal intensity varied according to the iron concentration of SPIO-labeled cells. Absorption spectrophotometry is both a highly sensitive and user-friendly technique that is feasible for quantifying the iron content of magnetically labeled cells. The presented data suggest that spectrophotometry is a promising tool for promoting the implementation of magnetic resonance-based cell tracking in routine clinical applications (from bench to bedside).     

Ultrasmall mixed ferrite colloids as multidimensional magnetic resonance imaging, cell labeling, and cell sorting agents

One area that has been overlooked in the evolution of magnetic nanoparticle technology is the possibility of introducing informational atoms into the iron oxide core of the coated colloid. Introduction of suitable atoms into the iron oxide core offers an opportunity to produce a quantifiable probe, thereby adding one or more dimensions to the magnetic colloid's informational status. Lanthanide-doped iron oxide nanoparticles have been synthesized to introduce informational atoms through the formation of colloidal mixed ferrites. These colloids are designated ultrasmall mixed ferrite iron oxides (USMIOs). USMIOs containing 5 mol % europium exhibit superparamagnetic behavior with an induced magnetization of 56 emu/g Fe at 1.5 T, a powder X-ray diffraction pattern congruent with magnetite, and R1 and R2 relaxivity values of 15.4 (mM s) (-1) and 33.9 (mM s) (-1), respectively, in aqueous solution at 37 degrees C and 0.47 T. USMIO can be detected by five physical methods, combining the magnetic resonance imaging (MRI) qualities of iron with the sensitive and quantitative detection of lanthanide metals by neutron activation analysis (NA), time-resolved fluorescence (TRF), X-ray fluorescence, along with detection by electron microscopy (EM). In addition to quantitative detection using neutron activation analysis, the presence of lanthanides in the iron oxide matrix confers attractive optical properties for long-term multilabeling studies with europium and terbium. These USMIOs offer high photostability, a narrow emission band, and a broad absorption band combining the high sensitivity of time-resolved fluorescence with the high spatial resolution of MRI. USMIO nanoparticles are prepared through modifications of traditional magnetite-based iron oxide colloid synthetic methods. A 5 mol % substitution of ferric iron with trivalent europium yielded a colloid with nearly identical magnetic, physical, and chemical characteristics to its magnetite colloid parent.     

Annexin V-CLIO: a nanoparticle for detecting apoptosis by MRI

Annexin V, which recognizes the phosphatidylserine of apoptotic cells, was conjugated to crosslinked iron oxide (CLIO) nanoparticles, a functionalized superparamagnetic preparation developed for target-specific magnetic resonance imaging (MRI). The resulting nanoparticle had an average of 2.7 annexin V proteins linked per CLIO nanoparticle through disulfide bonds. Using camptothecin to induce apoptosis, a mixture of Jurkat T cells (69% healthy and 31% apoptotic) was incubated with annexin V-CLIO and was applied to magnetic columns. The result was an almost complete removal of the apoptotic cells (> 99%). In a phantom MRI experiment, untreated control cells (12% apoptotic cells, 88% healthy cells) and camptothecin-treated cells (65% apoptotic cells, 35% healthy cells) were incubated with either annexin V-CLIO (1.0, 0.5, and 0.1 microgram Fe/mL) or with unlabeled CLIO. A significant signal decrease of camptothecin-treated cells relative to untreated cells was observed even at the lowest concentration tested. Unmodified CLIO failed to cause a significant signal change of apoptotic cells. Hence, annexin V-CLIO allowed the identification of cell suspensions containing apoptotic cells by MRI even at very low concentrations of magnetic substrate. Conjugation of annexin V to CLIO affords a strategy for the development of a MRI imaging probe for detecting apoptosis.     

"Clickable", trifunctional magnetite nanoparticles and their chemoselective biofunctionalization

A multifunctional iron oxide based nanoformulation for combined cancer-targeted therapy and multimodal imaging has been meticulously designed and synthesized using a chemoselective ligation approach. Novel superparamagnetic magnetite nanoparticles simultaneously functionalized with amine, carboxyl, and azide groups were fabricated through a sequence of stoichiometrically controllable partial succinylation and Cu (II) catalyzed diazo transfer on the reactive amine termini of 2-aminoethylphosphonate grafted magnetite nanoparticles (MNPs). Functional moieties associated with MNP surface were chemoselectively conjugated with rhodamine B isothiocyanate (RITC), propargyl folate (FA), and paclitaxel (PTX) via tandem nucleophic addition of amine to isothithiocyanates, Cu (I) catalyzed azide--alkyne click chemistry and carbodiimide-promoted esterification. An extensive in vitro study established that the bioactives chemoselectively appended to the magnetite core bequeathed multifunctionality to the nanoparticles without any loss of activity of the functional molecules. Multifunctional nanoparticles, developed in the course of the study, could selectively target and induce apoptosis to folate-receptor (FR) overexpressing cancer cells with enhanced efficacy as compared to the free drug. In addition, the dual optical and magnetic properties of the synthesized nanoparticles aided in the real-time tracking of their intracellular pathways also as apoptotic events through dual fluorescence and MR-based imaging.     

Hybrid,metal oxide-peptide amphiphile micelles for molecular magnetic resonance imaging of atherosclerosis

Background

Atherosclerosis, a major source of cardiovascular disease, is asymptomatic for decades until the activation of thrombosis and the rupture of enlarged plaques, resulting in acute coronary syndromes and sudden cardiac arrest. Magnetic resonance imaging (MRI) is a noninvasive nuclear imaging technique to assess the degree of atherosclerotic plaque with high spatial resolution and excellent soft tissue contrast. However, MRI lacks sensitivity for preventive medicine, which limits the ability to observe the onset of vulnerable plaques. In this study, we engineered hybrid metal oxide-peptide amphiphile micelles (HMO-Ms) that combine an inorganic, magnetic iron oxide or manganese oxide inner core with organic, fibrin-targeting peptide amphiphiles, consisting of the sequence CREKA, for potential MRI imaging of thrombosis on atherosclerotic plaques.

Results

Hybrid metal oxide-peptide amphiphile micelles, consisting of an iron oxide (Fe-Ms) or manganese oxide (Mn-Ms) core with CREKA peptides, were self-assembled into 20–30 nm spherical nanoparticles, as confirmed by dynamic light scattering and transmission electron microscopy. These hybrid nanoparticles were found to be biocompatible with human aortic endothelial cells in vitro, and HMO-Ms bound to human clots three to five times more efficiently than its non-targeted counterparts. Relaxivity studies showed ultra-high r₂ value of 457 mM^?1 s^?1 and r₁ value of 0.48 mM^?1 s^?1 for Fe-Ms and Mn-Ms, respectively. In vitro, MR imaging studies demonstrated the targeting capability of CREKA-functionalized hybrid nanoparticles with twofold enhancement of MR signals.

Conclusion

This novel hybrid class of MR agents has potential as a non-invasive imaging method that specifically detects thrombosis during the pathogenesis of atherosclerosis.

     

ENO1-targeted superparamagnetic iron oxide nanoparticles for detecting pancreatic cancer by magnetic resonance imaging

The aim of this study was to investigate in vitro magnetic resonance imaging (MRI) of PDAC using ENO1-targeted superparamagnetic iron oxide nanoparticles and xenograft models. Expression level and location of ENO1 protein in pancreatic cancer cell lines of CFPAC-1 and MiaPaCa-2 were detected by Western blotting, flow cytometry and confocal microscopy. Dex-g-PCL/SPIO nanoparticles targeting ENO1 were constructed with ENO1 antibody and characterized by MRI. In addition, ENO1-Dex-g-PCL/SPIO nanoparticles were tested to assess their efficacy on the detection of PDAC using in vitro and in vivo MRI. The results showed that ENO1 was expressed in both human PDAC cell lines of CFPAC-1 and MiaPaCa-2, demonstrating that the localization of cytoplasm and membrane was dominant. It was confirmed that ENO1 antibody was connected to the SPIO surface in ENO1-Dex-g-PCL/SPIO nanoparticles. The nanoparticles had satisfactory superparamagnetism and significantly enhance the detection of PDAC by in vivo and in vitro MRI. In conclusion, ENO1 can serve as a membrane protein expressed on human PDAC cell lines. ENO1-targeted SPIO nanoparticles using ENO1 antibody can increase the efficiency of detection of PDAC by in vitro and in vivo MRI.