Silica-coated Superparamagnetic Iron Research Articles

Silica-coated superparamagnetic iron oxide nanoparticles interacting with superoxide dismutase in the mouse primary hepatocytes

Given the great potential of superparamagnetic iron oxide nanoparticles (SPIONs) in the application of biomedical and water treatment fields, it is of vital significance to evaluate their toxicity and explore the underlying mechanism. Silica-coated SPIONs (SPIONs@SiO2) might generate oxidative stress and cytotoxicity by interfering antioxidant enzyme. This study investigated the response of superoxide dismutase (SOD) under SPIONs@SiO2-induced oxidative stress using a strategy integrating cellular and molecular methods. Results showed that intracellular SOD activity exhibited hormetic effects in response to SPIONs@SiO2-induced structural changes of SOD molecule and oxidative stress, which subsequently generated lipid oxidation and cell viability loss in the mouse primary hepatocytes. The structural changes and increasing activity of SOD molecule were resulted from the direct interaction with SPIONs@SiO2. Then, multi-spectroscopy, zeta potential measurements and isothermal titration calorimetry were used to study the interaction of SPIONs@SiO2 with SOD and the underlying mechanism. SOD interacts with SPIONs@SiO2 through electrostatic and hydrophobic forces, enhancing the hydrophobicity around Tyr 108. The enthalpy and entropy change of the interaction are 1.03 × 105 J.mol−1 and 474.6 J.mol−1.K−1, respectively, indicating the dominant driving forces are hydrophobic forces. The interaction led to the loosen of peptide chains and the reduction of aggregation state. And the α-helix content of SOD decreased to 13 % in the presence of SPIONs@SiO2.

Modular 3D printed flow system for efficient one-step synthesis of phenyl-functionalised silica-coated superparamagnetic iron oxide nanoparticles

Laminar flow regimes in 3D-printed reactors allow for the synthesis of Fe3O4 nanoparticles as well as subsequent coating and functionalisation with silica and phenyl, respectively.

Silica-Coated Superparamagnetic Iron Oxide Nanoparticles Ameliorate Leukoaraiosis-Triggered Oxidative Stress via Targeting of Nrf2 to Activate IRS-1/Akt Signals

This study mainly explored the amelioratory effect of silica-coated superparamagnetic iron oxide nanoparticles (SiO4@SPIONs) on leukoaraiosis-associated cognitive dysfunction via targeting of Nrf2 and their potential mechanism. PC12 cell line was given in vitro hypoxia-reoxygenation treatment (OGD/R) and divided into normal group, model group and SiO4@SPIONs treatment group. The cell survival rate, apoptosis rate, levels of ROS (reactive oxygen species), MDA (Malondialdehyde; malonic dialdehyde; Propanedial) and anti-oxidases were monitored. Western-blotting measured the level of Akt and Nrf2. The Akt-targeting antagonist LY294002 was applied for verifying the regulatory effect of SiO4@SPIONs. In comparison with normal cells, model cells exhibited significantly reduced viability, along with significantly elevated apoptosis rate. Meanwhile, model cells also displayed elevated levels of intracellular ROS and MDA, with diminished levels of SOD (Superoxide Dismutase), GSH (glutathione), CAT (Computerized Axial Tomography) and GSH-Px (glutathione peroxidase) which were accompanied by significantly weakened phosphorylation level of Akt. Lastly, model cells also exhibited moderate enhancement of Nrf2 and HO-1 expressions. Moreover, cells in SiO4@SPIONs treatment group exhibited significantly increased viability, along with reduced apoptosis rate. Meanwhile, the cells in the SiO4@SPIONs treatment group also displayed decreased levels of intracellular ROS and MDA, while showing increased levels of SOD, GSH, CAT and GSH-Px, which were accompanied by significantly increased Akt phosphorylation and Nrf2 and HO-1 expressions. The SiO4@SPIONS can ameliorate the leukoaraiosis-triggered oxidative stress via targeting of Nrf2 to activate the IRS-1/Akt signals.

Tubular electrosynthesis of silica-coated magnetite and evaluation of magnetic nanobiocatalyst efficacy during biomass hydrolysis.

Magnetic nanobiocatalysts (MNBCs) are a promising immobilization approach to ease enzyme recovery during bioprocessing. However, industrial adoption of MNBCs is unfeasible because MNBC-synthesis involves complex and potentially expensive processing steps including synthesis of silica-coated superparamagnetic iron oxide nanoparticles (Si-SPIONs). We developed a single-step process for Si-SPION synthesis using a tubular electrochemical system (TES) and investigated the effect of concentration of the Na2SiO3 coating agent on Si-SPION properties. The Si-SPIONs were used as a support for attachment of polymer-cellulase conjugate to make MNBCs. The spherical Si-SPIONs were 8-12nm in diameter including a 2-nm silica coating. Na2SiO3 concentration in the reactor did not affect Si-SPION morphology, but increasing Na2SiO3 concentration reduced SPION productivity in the reactor. Protective properties of the SPION silica coatings were demonstrated by showing that they prevented dissolution of SPIONs in an acid solution for 48h. Enzyme attachment was quantified as protein adsorption on Si-SPIONs which reached 55μg/mg Si-SPION. The MNBCs were recovered and reused four times. The use of TES for Si-SPION synthesis is promising to reduce MNBC production complexity.

Oleic Acid Protects Endothelial Cells from Silica-Coated Superparamagnetic Iron Oxide Nanoparticles (SPIONs)-Induced Oxidative Stress and Cell Death.

Superparamagnetic iron oxide nanoparticles (SPIONs) have great potential for use in medicine, but they may cause side effects due to oxidative stress. In our study, we investigated the effects of silica-coated SPIONs on endothelial cells and whether oleic acid (OA) can protect the cells from their harmful effects. We used viability assays, flow cytometry, infrared spectroscopy, fluorescence microscopy, and transmission electron microscopy. Our results show that silica-coated SPIONs are internalized by endothelial cells, where they increase the amount of reactive oxygen species (ROS) and cause cell death. Exposure to silica-coated SPIONs induced accumulation of lipid droplets (LD) that was not dependent on diacylglycerol acyltransferase (DGAT)-mediated LD biogenesis, suggesting that silica-coated SPIONs suppress LD degradation. Addition of exogenous OA promoted LD biogenesis and reduced SPION-dependent increases in oxidative stress and cell death. However, exogenous OA protected cells from SPION-induced cell damage even in the presence of DGAT inhibitors, implying that LDs are not required for the protective effect of exogenous OA. The molecular phenotype of the cells determined by Fourier transform infrared spectroscopy confirmed the destructive effect of silica-coated SPIONs and the ameliorative role of OA in the case of oxidative stress. Thus, exogenous OA protects endothelial cells from SPION-induced oxidative stress and cell death independent of its incorporation into triglycerides.

Folic acid conjugated PAMAM-modified mesoporous silica-coated superparamagnetic iron oxide nanoparticles for potential cancer therapy

In this study, novel folate-receptor-targeted polyamidoamine (PAMAM) dendrimer functional mesoporous silica-coated magnetic nanoparticles were prepared for drug delivery agents for photodynamic therapy applications. The surface of the magnetic nanoparticles was coated with mesoporous silica (M-MSN). The M-MSN nanoparticles were functionalized with siloxane-cored PAMAM dendrons (generation 1 to 3). The surface of the M-MSN-PAMAM nanocarriers was targeted with folic acid. Indocyanine green (ICG) a near-infrared dye was loaded in the M-MSN-PAMAM nanocarriers and the photodynamic therapy efficiency of the drug-loaded nanocarriers was evaluated on MCF-7 cells.MCF-7 cells were subjected to tissue culture E-Plate that was used to generate dynamic real-time data by measuring electrical impedance across interdigitated microelectrodes on the bottom of the plate. Light source (LEDs) was designed as a system that fit 96 well-plate and cells were irradiated at 785 nm for 20 min. Also, these results were confirmed by WST-1 assay in dark and light conditions for MCF-7 cells. The results showed that in vitro application of ICG loaded M-MSN-PAMAM-FA causes apoptosis in the MCF-7 cell line.

A novel intratumoral pH/redox-dual-responsive nanoplatform for cancer MR imaging and therapy

The integration of diagnostic and therapeutic functions in a nanoplatform has been a rapidly emerging method in the management of cancer. The application of imaging technology paves the way to track the pharmacokinetics of the nanoplatforms, to guide the treatment, and to monitor the therapeutic processes and outcomes. Herein, we reported a novel type of monodisperses mesoporous silica-coated superparamagnetic iron oxide-based multifunctional nanoplatform (DOX@MMSN-SS-PEI-cit) for the diagnosis and treatment of cancer. The fabrication process included the surface modification of monodisperses mesoporous silica nanoparticle (MMSN) with branched polyethyleneimine (PEI) via disulfide bonds and the further coupling of citraconic anhydride to PEI. Typically, the hydrolysis of amide bonds in the tumor microenvironment (TME) could lead to a negative-to-positive charge reversion, which can enhance the endosomal escape of the resulting nanoplatform. The rapid release of doxorubicin hydrochloride (DOX) directly killed the cancer cells. Due to the superparamagnetic iron oxide-based high-resolution T2-weighted MR imaging contrast agents, this novel multifunctional nanoplatform successfully realized MR imaging, targeted drug delivery and controlled release in one system, and achieved significant improvement in tumor diagnosis and therapy. In summary, the therapeutic nanoplatform is a promising option in precise cancer treatment.

Biocompatibility assessment of sub-5 nm silica-coated superparamagnetic iron oxide nanoparticles in human stem cells and in mice for potential application in nanomedicine.

Ultrasmall superparamagnetic iron oxide nanoparticles with a size <5 nm are emerging nanomaterials for their excellent biocompatibility, chemical stability, and tunable surface modifications. The applications explored include dual-modal or multi-modal imaging, drug delivery, theranostics and, more recently, magnetic resonance angiography. Good biocompatibility and biosafety are regarded as the preliminary requirements for their biomedical applications and further exploration in this field is still required. We previously synthesized and characterized ultrafine (average core size of 3 nm) silica-coated superparamagnetic iron oxide fluorescent nanoparticles, named sub-5 SIO-Fl, uniform in size, shape, chemical properties and composition. The cellular uptake and in vitro biocompatibility of the as-synthesized nanoparticles were demonstrated in a human colon cancer cellular model. Here, we investigated the biocompatibility of sub-5 SIO-Fl nanoparticles in human Amniotic Mesenchymal Stromal/Stem Cells (hAMSCs). Kinetic analysis of cellular uptake showed a quick nanoparticle internalization in the first hour, increasing over time and after long exposure (48 h), the uptake rate gradually slowed down. We demonstrated that after internalization, sub-5 SIO-Fl nanoparticles neither affect hAMSC growth, viability, morphology, cytoskeletal organization, cell cycle progression, immunophenotype, and the expression of pro-angiogenic and immunoregulatory paracrine factors nor the osteogenic and myogenic differentiation markers. Furthermore, sub-5 SIO-Fl nanoparticles were intravenously injected into mice to investigate the in vivo biodistribution and toxicity profile for a time period of 7 weeks. Our findings showed an immediate transient accumulation of nanoparticles in the kidney, followed by the liver and lungs, where iron contents increased over a 7-week period. Histopathology, hematology, serum pro-inflammatory response, body weight and mortality studies demonstrated a short- and long-term biocompatibility and biosafety profile with no apparent acute and chronic toxicity caused by these nanoparticles in mice. Overall, these results suggest the feasibility of using sub-5 SIO-Fl nanoparticles as a promising agent for stem cell magnetic targeting as well as for diagnostic and therapeutic applications in oncology.

Intracellular processing of silica-coated superparamagnetic iron nanoparticles in human mesenchymal stem cells.

Silica-coated superparamagnetic iron nanoparticles (SiMAGs) are an exciting biomedical technology capable of targeted delivery of cell-based therapeutics and disease diagnosis. However, in order to realise their full clinical potential, their intracellular fate must be determined. The analytical techniques of super-resolution fluorescence microscopy, particle counting flow cytometry and pH-sensitive nanosensors were applied to elucidate mechanisms of intracellular SiMAG processing in human mesenchymal stem cell (hMSCs). Super-resolution microscopy showed SiMAG fluorescently-tagged nanoparticles are endocytosed and co-localised within lysosomes. When exposed to simulated lysosomal conditions SiMAGs were solubilised and exhibited diminishing fluorescence emission over 7 days. The in vitro intracellular metabolism of SiMAGs was monitored in hMSCs using flow cytometry and co-localised pH-sensitive nanosensors. A decrease in SiMAG fluorescence emission, which corresponded to a decrease in lysosomal pH was observed, mirroring ex vivo observations, suggesting SiMAG lysosomal exposure degrades fluorescent silica-coatings and iron cores. These findings indicate although there is a significant decrease in intracellular SiMAG loading, sufficient particles remain internalised (>50%) to render SiMAG treated cells amenable to long-term magnetic cell manipulation. Our analytical approach provides important insights into the understanding of the intracellular fate of SiMAG processing, which could be readily applied to other particle therapeutics, to advance their clinical translation.

Macrophage entrapped silica coated superparamagnetic iron oxide particles for controlled drug release in a 3D cancer model

Targeted delivery of drugs is a major challenge in treatment of diverse diseases. Systemically administered drugs demand high doses and are accompanied by poor selectivity and side effects on non-target cells. Here, we introduce a new principle for targeted drug delivery. It is based on macrophages as transporters for nanoparticle-coupled drugs as well as controlled release of drugs by hyperthermia mediated disruption of the cargo cells and simultaneous deliberation of nanoparticle-linked drugs. Hyperthermia is induced by an alternating electromagnetic field (AMF) that induces heat from silica-coated superparamagnetic iron oxide nanoparticles (SPIONs). We show proof-of-principle of controlled release by the simultaneous disruption of the cargo cells and the controlled, AMF induced release of a toxin, which was covalently linked to silica-coated SPIONs via a thermo-sensitive linker. Cells that had not been loaded with SPIONs remain unaffected. Moreover, in a 3D co-culture model we demonstrate specific killing of associated tumour cells when employing a ratio as low as 1:40 (SPION-loaded macrophage: tumour cells). Overall, our results demonstrate that AMF induced drug release from macrophage-entrapped nanoparticles is tightly controlled and may be an attractive novel strategy for targeted drug release.

Phagocytosis and Cytotoxicity Analysis of Thioflavin-T Doped Silica-Coated Superparamagnetic Iron Oxide Nanoparticles Bound to Amyloid Beta 1–42

With superparamagnetic iron oxide nanoparticles (SPIONs) increasingly attracting interest in life sciences, especially in applications such as cancer or Alzheimer's disease, the need for in vitro and in vivo investigation of their behavior, when taken up by structures of the immune system, becomes imperative. In this letter, thioflavin-T tagged core-shell SPIONs bound to amyloid beta 1–42 (A β 1-42) were imbued into macrophages in order to fully understand the effect of phagocytosis on functionalized T-SPIONs and cellular structures. Results after 24 h of exposure in macrophage cultures at various concentrations of T-SPIONs (both free and bound) indicate that the material is successfully phagocytosed, with an uptake above 60%, and cannot be considered cytotoxic, as proven by both tetrazole MTT colorimetric assays and trypan blue measurements. Concurrently, it does not affect the prooxidant–antioxidant balance in the cell culture. Taking into consideration that Α β 1-42 dissolves during phagocytosis, whereas the magnetic and fluorescent character of the silica-coated nanoparticles is maintained after a second phagocytosis cycle, a reuse process of T-SPIONs seems feasible, presenting multiple advantages.

Soybean peroxidase immobilized onto silica-coated superparamagnetic iron oxide nanoparticles: Effect of silica layer on the enzymatic activity

Peroxidase immobilization onto magnetic supports is considered an innovative strategy for the development of technologies that involves enzymes in wastewater treatment. In this work, magnetic biocatalysts were prepared by immobilization of soybean peroxidase (SBP) onto different silica-coated superparamagnetic iron oxide nanoparticles. The obtained magnetic biocatalysts were tested for the degradation of malachite green (MG), a pollutant often found in industrial wastewaters and with significant drawbacks for the human and environmental health. A deep physicochemical characterization of the materials was performed by means of X-ray diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), High Resolution-Transmission Electron Microscope (HR-TEM) and magnetization measurements among others techniques. Results showed high immobilization yield of SBP onto nanomaterials with excellent properties for magnetic recoverability. A partial loss of activity with respect to free SBP was observed, compatible with the modification of the conformational structure of the enzyme after immobilization. The structural modification depended on the amount (and thickness) of silica present in the hybrid materials and the activity yield of 43% was obtained for the best biocatalyst. Thermal stability and reusability capacity were also evaluated.

Efficient one-pot sonochemical synthesis of thickness-controlled silica-coated superparamagnetic iron oxide (Fe3O4/SiO2) nanospheres

A facile and eco-friendly efficient sonochemical approach was designed for the synthesis of highly crystalline Fe3O4 and Fe3O4/SiO2 core/shell nanospheres in single reaction. The generated physical properties (shock waves, microjets, and turbulent flows) from ultrasonication as a consequence of the collapse of microbubbles and polyvinylpyrrolidone (PVP) as a chemical linker were found to play a crucial role in the successful formation of the core/shell NPs within short time than the previously reported methods. Transmission electron microscopy revealed that a uniform SiO2 shell is successfully coated over Fe3O4 nanospheres, and the thickness of the silica shell could be easily controlled in the range from 5 to 15 nm by adjusting the reaction parameters. X-ray diffraction data were employed to confirm the formation of highly crystalline and pure phase of a cubic inverse spinel structure for magnetite (Fe3O4) nanospheres. The magnetic properties of the as-synthesized Fe3O4 and Fe3O4/SiO2 core/shell nanospheres were measured at room temperature using vibrating sample magnetometer, and the results demonstrated a high magnetic moment values with superparamagnetic properties.

An efficient synthesis of naphtho[2,1-b]furan-2(1H)-ones catalysed by Nafion-H supported on silica-coated super paramagnetic iron oxide nanoparticles

A one-pot procedure is descibed for the synthesis of naphtho[2,1- b]furan-2(1 H)-ones via a multicomponent reaction of aryl aldehydes, hippuric acid, acetic anhydride and β-naphthol in the presence of Nafion-H supported on silica-coated superparamagnetic iron oxide nanoparticles under microwave irradiation. The catalyst can be recovered easily and reused several times without significant loss of catalytic activity.

Harmful at non-cytotoxic concentrations: SiO2-SPIONs affect surfactant metabolism and lamellar body biogenesis in A549 human alveolar epithelial cells

The pulmonary delivery of nanoparticles (NPs) is a promising approach in nanomedicine. For the efficient and safe use of inhalable NPs, understanding of NP interference with lung surfactant metabolism is needed. Lung surfactant is predominantly a phospholipid substance, synthesized in alveolar type II cells (ATII), where it is packed in special organelles, lamellar bodies (LBs). In vitro and in vivo studies have reported NPs impact on surfactant homeostasis, but this phenomenon has not yet been sufficiently examined. We showed that in ATII-like A549 human lung cancer cells, silica-coated superparamagnetic iron oxide NPs (SiO2-SPIONs), which have a high potential in medicine, caused an increased cellular amount of acid organelles and phospholipids. In SiO2-SPION treated cells, we observed elevated cellular quantity of multivesicular bodies (MVBs), organelles involved in LB biogenesis. In spite of the results indicating increased surfactant production, the cellular quantity of LBs was surprisingly diminished and the majority of the remaining LBs were filled with SiO2-SPIONs. Additionally, LBs were detected inside abundant autophagic vacuoles (AVs) and obviously destined for degradation. We also observed time- and dose-dependent changes in mRNA expression for proteins involved in lipid metabolism. Our results demonstrate that non-cytotoxic concentrations of SiO2-SPIONs interfere with surfactant metabolism and LB biogenesis, leading to disturbed ability to reduce hypophase surface tension. To ensure the safe use of NPs for pulmonary delivery, we propose that potential NP interference with LB biogenesis is obligatorily taken into account.

Drug-loaded liposome-capped mesoporous core-shell magnetic nanoparticles for cellular toxicity study.

Liposome-capped core-shell mesoporous silica-coated superparamagnetic iron oxide nanoparticles called 'magnetic protocells' were prepared as novel nanocomposites and used for loading anticancer drug doxorubicin (DOX) for cellular toxicity study. Cytotoxicity of the magnetic protocells with or without DOX was tested in vitro on commercial MCF7 and U87 cell lines under alternating magnetic field. MCF7 cell line treated with the DOX-loaded nanoparticles under alternating magnetic field exhibited nearly 20% lower survival rate after 24 h compared with cells treated with free DOX and similarly, it was around 24% when applied to U87. The results indicate that the magnetic protocells could be useful for future cancer treatment in vivo by the combination of targeted drug delivery and magnetic hyperthermia.

A smart fluorescence nanoprobe for the detection of cellular alkaline phosphatase activity and early osteogenic differentiation

In the past decades, biomaterials were designed to induce stem cell toward osteogenic differentiation. However, conventional methods for evaluation osteogenic differentiation all required a process of cell fixation or lysis, which induce waste of a large number of cells. In this study, a fluorescence nanoprobe was synthesized by combining phosphorylated fluoresceinamine isomer I (FLA) on the surface of mesoporous silica-coated superparamagnetic iron oxide (Fe3O4@mSiO2) nanoparticles. In the presence of alkaline phosphatase (ALP), the phosphorylated FLA on the nanoprobe would be hydrolyzed, resulting in a fluorescence recovery of FLA. During early osteogenic differentiation, a high-level expression of cellular ALP was induced, which accelerated the hydrolysis of phosphorylated FLA, resulting in an enhancement of cellular fluorescence intensity. This fluorescence nanoprobe provides us a rapid and non-toxic method for the detection of cellular ALP activity and early osteogenic differentiation.

In vitro toxicity screening of silica-coated superparamagnetic iron oxide nanoparticles in glial cells

This work was supported by Xunta de Galicia (EM 2012/079), the project NanoToxClass (ERA ERASIINN/001/2013) [funded by FCT/MCTES (PIDDAC) and co-funded by the European Regional Development Fund (ERDF) through the COMPETE Programme], and by TD1204 MODENA COST Action.

Shape-switching microrobots for medical applications: the influence of shape in drug delivery and locomotion.

The effect of dynamic shape switching of hydrogel bilayers on the performance of self-folding microrobots is investigated for navigation in body orifices and drug release on demand. Tubular microrobots are fabricated by coupling a thermoresponsive hydrogel nanocomposite with a poly(ethylene glycol)diacrylate (PEGDA) layer, to achieve spontaneous and reversible folding from a planar rectangular structure. Graphene oxide (GO) or silica-coated superparamagnetic iron oxide nanoparticles are dispersed in the thermoresponsive hydrogel matrix to provide near-infrared (NIR) light sensitivity or magnetic actuation, respectively. The NIR light-responsive microstructures are fabricated for triggered drug delivery while magnetic nanocomposite-based microrobots are used to analyze the role of shape in locomotion. Experimental analysis and computational simulations of tubular structures show that drug release and motility can be optimized through controlled shape change. These concepts are finally applied to helical microrobots to show a possible way to achieve autonomous behavior.

Silica-coated super-paramagnetic iron oxide nanoparticles (SPIONPs): a new type contrast agent of T1 magnetic resonance imaging (MRI).

Magnetic resonance imaging (MRI), a sophisticated promising three-dimensional tomographic noninvasive diagnostic technique, has an intrinsic advantage in safety compared with radiotracer and optical imaging modalities; however, MRI contrast agents are less sensitive than complexes used in other imaging techniques. Usually the clinically used Gd-based complexes MRI-T1 contrast agents are toxic; therefore, the demand for nontoxic novel T1-weighted MRI candidates with ultrasensitive imaging and advanced functionality is very high. In this research, silica-coated ultra-small monodispersed super-paramagnetic iron oxide nanoparticles were synthesized via a thermal decomposition method, which demonstrated themselves as a high performance T1-weighted MRI contrast agent for heart, liver, kidney and bladder based on in vivo imaging analyses. Transmission electron microscopy (TEM) results illustrated that the diameter of the SPIONPs was in the range of 4 nm and the average size of Fe3O4@SiO2 was about 30-40 nm. X-ray diffraction (XRD) and Raman spectroscopy analyses revealed the phase purity of the prepared SPIONPs. These magnetite nanoparticles exhibited a weak magnetic moment at room temperature because of the spin-canting effect, which promoted a high positive signal enhancement ability. MTT assays and histological analysis demonstrated good biocompatibility of the SPIONPs in vitro and in vivo. In addition, the silica-coated ultra-small (4 nm sized) magnetite nanoparticles exhibited a good r1 relaxivity of 1.2 mM-1 s-1 and a low r2/r1 ratio of 6.5 mM-1 s-1. In vivo T1-weighted MR imaging of heart, liver, kidney and bladder in mice after intravenous injection of nanoparticles further verified the high sensitivity and biocompatibility of the as-synthesized magnetite nanoparticles. These results reveal silica-coated SPIONPs as a promising candidate for a T1 contrast agent with extraordinary capability to enhance MR images.