Presence Of Superparamagnetic Iron Oxide Nanoparticles Research Articles

Enhanced 129 Xe T1 relaxation in whole blood and in the presence of SPIONs at low magnetic field strengths.

To compare the effect of superparamagnetic iron oxide nanoparticles (SPIONs) on the T1 of 129 Xe and 1 H and to measure the relaxation of 129 Xe in blood at low and high magnetic field strengths. 129 Xe and 1 H T1 relaxometry was performed at low- and high-field strengths in samples containing different SPION concentrations, while imaging was used to compare the contrast obtainable in these two field regimes. In vivo experiments at variable field strengths were performed to determine the depolarization of 129 Xe in blood and the feasibility of in vivo dissolved-phase spectroscopy and imaging at low field. The SPION relaxivity was substantially greater at low field for 1 H, increasing from 0.92 ± 0.06 mM s-1 at 11.7T to 31.5 ± 1.8 mM s-1 at 0.6 mT, and for 129 Xe, which increased from 0.13 ± 0.03 mM s-1 at 11.7T to 7.32 ± 0.71 mM s-1 at 2.1 mT. The additional MR signal loss increased from 0.7% at 9.4T to 20.6 ± 4.2% at 0.6 mT for 1 H and from -0.7 ± 3.4% at 9.4T to 12.7 ± 3.5% at 2.1 mT for 129 Xe. Blood was found to depolarize 129 Xe below 3T in a manner inversely proportional to the field strength. In vitro studies at 2.1 mT suggest 129 Xe relaxation times below 5s in blood dilutions as low as 0.4% volume. SPIONs longitudinal relaxivity increases at low field both for 1 H and 129 Xe. The depolarization of xenon in blood, which is found to increase below 3T, effectively prevents in vivo dissolved-phase spectroscopy and imaging at low-field strengths.

Highly Sensitive and High-Throughput Magnetic Resonance Thermometry of Fluids Using Superparamagnetic Nanoparticles

Magnetic resonance imaging (MRI) enables noninvasive three-dimensional thermometry, which has potential applications in biological tissues and engineering systems. In biological tissues, where MRI is routinely used to monitor temperature during thermal therapies, ${T}_{1}$ or ${T}_{2}$ contrast in water are relatively insensitive to temperature, and techniques with greater temperature sensitivity, such as chemical shift or diffusion imaging, suffer from motional artifacts and long scan times. MR thermometry is not well developed for nonbiological or engineering systems. We describe an approach for highly sensitive and high-throughput MR thermometry that is not susceptible to motional artifacts and could be applied to various biological systems and engineering fluids. We use superparamagnetic iron-oxide nanoparticles (SPIONs) to spoil ${T}_{2}$ of water protons. Motional narrowing results in proportionality between ${T}_{2}$ and the diffusion constant, dependent only on the temperature in a specific environment. Our results show, for pure water, the nuclear magnetic resonance linewidth and ${T}_{2}$ follow the same temperature dependence as the self-diffusion constant of water. Thus, a ${T}_{2}$ mapping is a diffusion mapping in the presence of SPIONs, and ${T}_{2}$ is a thermometer. For pure water, a ${T}_{2}$ mapping of a 64 \ifmmode\times\else\texttimes\fi{} 64 image (voxel size = 0.5 mm \ifmmode\times\else\texttimes\fi{} 0.5 mm \ifmmode\times\else\texttimes\fi{} 3 mm) in a 9.4 T MRI scanner resulted in a temperature resolution of 0.5 K for a scan time of 2 min. This indicates a highly sensitive and high-throughput MR thermometry technique that potentially has a range of applications from thermal management fluids to biological tissues.

Iron oxide nanoparticle encapsulated; folic acid tethered dual metal organic framework-based nanocomposite for MRI and selective targeting of folate receptor expressing breast cancer cells

Metal organic frameworks (MOFs) have been used as an efficient carrier for many therapeutic agents for cancer due to their unique properties. Even though numerous discrete MOFs have been used for biomedical applications, the traditional MOF-based composites are mainly limited to the solitary MOF source and functionalities. Herein, we report a novel and facile strategy for the design and fabrication of iron oxide (IO) nanoparticle encapsulated dual MOF composite, decorated with folic acid (FA) as targeting agent and Quercetin (Q) as drug payload. Due to the presence of superparamagnetic IO nanoparticles, the composites inherently show the potential usage for magnetic resonance imaging (MRI). By integrating dual MOFs (ZIF-8/ZIF-67) with the targeting agents and drug the resultant nanocomposites (IO/Z8-Z67/FA/Q) exhibited effective anticancer activities on FA receptor-positive breast cancer cell culture model (MDA-MB-231). The IO/Z8-Z67/FA/Q nanocomposite enhanced apoptosis and cytotoxicity in the MDA-MB-231 cell line (expressing folate receptors) as compared to the MCF-7 cell line (lacking the folate receptors). The uptake analysis of the nanocomposite was also carried out using flow cytometry to confirm FA targeting. Mechanistically, the folate receptor targeted IO/Z8-Z67/FA/Q nanocomposite delivery to MDA-MB-231 cells caused high ROS generation and nuclear fragmentation, leading to cell death. The results indicate that the IO/Z8-Z67/FA/Q can be a potential theranostics agent for effective cancer therapy and targeting. The proposed IO/Z8-Z67/FA composite was also used to load another anticancer drug like 5-fluorouracil (5FU) and cytotoxicity results show promising outcomes suggesting the current nanocomposite as all-purpose drug delivery carrier.

Superparamagnetic Iron Oxide Nanoparticles (SPIONs) Loaded with miR-29a Improve Efficacy of Chemotherapy in Hepatocellular Carcinoma

Development of hepatic artery chemoembolization technology effectively improves outcome of hepatocellular carcinoma (HCC), but it is still not the first-line option. This study aimed to explore therapeutic potential of superparamagnetic iron oxide nanoparticles (SPIONs) in the treatment of HCC. After establishment of miR-29aloaded SPIONs, HCC cells were co-cultured with composite nanoparticles or infected with lentivirus expressing miR-29a, and then exposed to X-ray at a dose of 0.2 Gy/day. MTT, flow cytometry and colony formation experiments were carried out to determine proliferation, apoptosis and colony forming ability of HCC cells. Animal experiments were set up through hepatic artery perfusion to assess the in vivo effect of miR-29aloaded SPIONs on tumor growth. Both miR-29a-loaded SPIONs and miR-29a-loaded nanoparticles decreased proliferation and migration of HCC cells, enhancing sensitivity of cells to chemotherapy, whilst SPIONs exhibited more significant effect and significantly suppressed tumor growth. The presence of SPIONs decreased clone formation and hindered cell cycle progression of HCC cells. This study confirmed that miR-29a-loaded SPIONs suppress malignant characteristics of HCC cells and sensitize cells to chemotherapy, improving the efficacy of treatment, which provides a potential alternative for targeted chemotherapy of HCC.

Alginate-magnetic short nanofibers 3D composite hydrogel enhances the encapsulated human olfactory mucosa stem cells bioactivity for potential nerve regeneration application

The design of 3D hydrogel constructs to elicit highly controlled cell response is a major field of interest in developing tissue engineering. The bioactivity of encapsulated cells inside pure alginate hydrogel is limited by its relatively inertness. Combining short nanofibers within a hydrogel serves as a promising method to develop a cell friendly environment mimicking the extracellular matrix. In this paper, we fabricated alginate hydrogels incorporating different magnetic short nanofibers (M.SNFs) content for olfactory ecto-mesenchymal stem cells (OE-MSCs) encapsulation. Wet-electrospun gelatin and superparamagnetic iron oxide nanoparticles (SPIONs) nanocomposite nanofibers were chopped using sonication under optimized conditions and subsequently embedded in alginate hydrogels. The storage modulus of hydrogel without M.SNFs as well as with 1 and 5 mg/mL of M.SNFs were in the range of nerve tissue. For cell encapsulation, OE-MSCs were used as a new hope for neuronal regeneration due to their neural crest origin. Resazurin analyses and LIVE/DEAD staining confirmed that the composite hydrogels containing M.SNFs can preserve the cell viability after 7 days. Moreover, the proliferation rate was enhanced in M.SNF/hydrogels compared to alginate hydrogel. The presence of SPIONs in the short nanofibers can accelerate neural-like differentiation of OE-MSCs rather than the sample without SPIONs.

Ultra Short Echo Time MRI of Iron-Labelled Mesenchymal Stem Cells in an Ovine Osteochondral Defect Model

Multipotent Mesenchymal Stem/Stromal Cells (MSCs) are widely used in cellular therapy for joint repair. However, the use of MSC therapies is complicated by a lack of understanding of the behaviour of cells and repair within the joint. Current methods of MSC tracking include labelling the cells with Super Paramagnetic Iron Oxide nanoparticles (SPIOs). However, standard acquisition sequences (T2 and T2*) give poor anatomical definition in the presence of SPIOs. To avoid anatomical compromise in the presence of SPIOs, we have investigated the use of Ultra-short Echo Time (UTE) MRI, using a 3D cones acquisition trajectory. This method was used to track SPIO labelled MSC injected into joints containing osteochondral defects in experimental sheep. This study demonstrates that multiple echo times from UTE with 3 T MRI can provide excellent anatomical detail of osteochondral defects and demonstrate similar features to histology. This work also monitors the location of SPIO-labelled cells for regenerative medicine of the knee with MRI, histology, and Prussian blue staining. With these methods, we show that the SPIOs do not hone to the site of defect but instead aggregate in the location of injection, which suggests that any repair mechanism with this disease model must trigger a secondary process.

Related physicochemical, rheological, and dielectric properties of nanocomposites of superparamagnetic iron oxide nanoparticles with polyethyleneglycol

ABSTRACTIn this study, we present the physicochemical, rheological, and dielectric properties of the superparamagnetic iron oxide nanoparticles (SPIONs) coated with polyethyleneglycol (PEG). It was observed that the increase of the concentration of PEG prohibited the sedimentation of nanoparticles, which increased the colloidal stability of nanocomposites. The surface study of the polymer and the nanocomposites using TOF‐SIMS showed that the samples did not have the same surface properties. The analysis of the intensity ratios of the FeO+/Fe+ and OH−/O− peaks of the nanocomposites of bare, positively, and negatively charged SPIONs with PEG revealed that no reduction occurred for these nanoparticles when coated with PEG, whereas the iron atoms on the surface of PEG negatively charged SPIONs were less oxidized than those on the surface of PEG‐bare SPIONs, and the iron atoms on the surface of PEG positively charged SPIONs were more oxidized than the second ones. The rheological study of the polymer and the nanocomposites revealed that the presence of SPIONs did not change the rheological behavior of PEG. The analysis of the dielectric properties of PEG and its composites with SPIONs showed that when SPIONs particles (bare and positively charged) were included in PEG, low frequency dispersion (LFD) was strongly enhanced, that the iron oxide nanoparticles reduced the impedance of PEG in the nanocomposites and that the difference in their surface charge affected their impedance. Taken together, these results suggest that the nanocomposites of PEG with SPIONs have appropriate properties for fluid modification and applications in the nanotechnology and photovoltaic devices. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48280.

Superparamagnetic iron oxide nanoparticles (SPIONs) modulate hERG ion channel activity

Superparamagnetic iron oxide nanoparticles (SPIONs) are widely used in various biomedical applications, such as diagnostic agents in magnetic resonance imaging (MRI), for drug delivery vehicles and in hyperthermia treatment of tumors. Although the potential benefits of SPIONs are considerable, there is a distinct need to identify any potential cellular damage associated with their use. Since human ether à go-go-related gene (hERG) channel, a protein involved in the repolarization phase of cardiac action potential, is considered one of the main targets in the drug discovery process, we decided to evaluate the effects of SPIONs on hERG channel activity and to determine whether the oxidation state, the dimensions and the coating of nanoparticles (NPs) can influence the interaction with hERG channel. Using patch clamp recordings, we found that SPIONs inhibit hERG current and this effect depends on the coating of NPs. In particular, SPIONs with covalent coating aminopropylphosphonic acid (APPA) have a milder effect on hERG activity. We observed that the time-course of hERG channel modulation by SPIONs is biphasic, with a transient increase (∼20% of the amplitude) occurring within the first 1–3 min of perfusion of NPs, followed by a slower inhibition. Moreover, in the presence of SPIONs, deactivation kinetics accelerated and the activation and inactivation I–V curves were right-shifted, similarly to the effect described for the binding of other divalent metal ions (e.g. Cd2+ and Zn2+). Finally, our data show that a bigger size and the complete oxidation of SPIONs can significantly decrease hERG channel inhibition. Taken together, these results support the view that Fe2+ ions released from magnetite NPs may represent a cardiac risk factor, since they alter hERG gating and these alterations could compromise the cardiac action potential.

Inhibitive effect of super paramagnetic iron oxide nanoparticles on the alkaline hydrolysis of procaine

The Super Paramagnetic Iron Oxide Nanoparticles (SPIONs) can bind drugs and act as drug-carriers. The magnetically active SPIONs can be used to deliver the drugs to the target through magnetic fields. The objective of the present work has been undertaken to study the stability, and binding behaviour of procaine with SPIONs and surfactant-coated SPIONs. Procaine is among the ester drugs and hydrolyses in the alkaline medium. The influence of SPIONs and surfactant-coated SPIONs on the rate of hydrolysis of procaine in alkaline medium may help to define the behaviour of the drug in the presence of these nanoparticles. The kinetic studies of procaine hydrolysis in the presence of SPIONs and surfactant-coated SPIONs were carried out spectrophotometrically. The concentrations of OH− ions were taken in excess over [procaine] to keep the reaction conditions under pseudo-first-order. The presence of SPIONs and the SPIONs coated with cetyltrimethylammonium bromide; CTABr and sodium dodecylsulphate; SDS surfactants displayed an inhibitive effect on the rate of hydrolysis of procaine. The synthesised nanoparticles were characterised using X-ray diffraction (XRD), scanning electron microscopy (SEM), vibrating sample magnetometer (VSM), transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FTIR). The kψ-[surfactant] profile in the presence of SPIONs was discussed using the pseudophase model in which the reactants are considered to be distributed in the aqueous and micellar media. The rate constant for the procaine hydrolysis and the binding constants of procaine with coated and non-coated SPIONs have been calculated by analysing the data for the variation in the rate constant with the change in [surfactant], [SPIONs] and [surfactant-coated SPIONs].Graphic abstractThe studies on the rate of hydrolysis of procaine in the presence of SPIONs and surfactant-coated SPIONs shows inhibitive effects of NPs on the reaction. Procaine has good binding affinity with surfactant-coated SPIONs in comparison with the bare SPIONs.

Combining Inulin Multifunctional Polycation and Magnetic Nanoparticles: Redox-Responsive siRNA-Loaded Systems for Magnetofection.

Superparamagnetic Iron Oxide Nanoparticles (SPIONs) are recognized as one of the most promising agents for theranostic applications. Among methods designed for siRNA delivery, magnetofection, that is, nucleic acid cell uptake under the influence of a magnetic field acting on magnetic nucleic acid vectors, is emerging as a unique approach to combining advantages such as strong improvement of the kinetics of the delivery process and the possibility of localizing nucleic acid delivery to an area where the magnetic field is applied. This paper reports on the preparation of siRNA loaded magnetoplexes—named ICD@SS@SPIONs/siRNA—by controlled crosslinking, in the presence of SPIONs, of the polycation INU-C-DETA, synthesized starting from the polysaccharide inulin by grafting diethylenetriamine and cystamine molecules. The obtained ICD@SS@SPIONs/siRNA have suitable chemical-physical characteristics to be employed for iv administration and are also able to release siRNA in a redox-triggered manner thanks to intracellular glutathione (GSH) mediated reduction of disulphide bridges formed during the crosslinking process. Moreover, ICD@SS@SPIONs/siRNA are able to produce magnetic targeting in vitro on breast cancer cells, without appreciable cyto- and hemo-toxic effects, in a wide range of concentrations. Finally, protein binding to nanoparticles revealed that obtained systems are potentially longer circulating and applicable as a smart multifunctional agents for cancer therapy.

The enhanced HIFU-induced thermal effect via magnetic ultrasound contrast agent microbubbles

High intensity focused ultrasound (HIFU) has been regarded as a promising technology for treating cancer and other severe diseases noninvasively. In the present study, dual modality magnetic ultrasound contrast agent microbubbles (MBs) were synthesized by loading the super paramagnetic iron oxide nanoparticles (SPIOs) into the albumin-shelled MBs (referred as SPIO-albumin MBs). Then, both experimental measurements and numerical simulations were performed to evaluate the ability of SPIO-albumin MBs of enhancing HIFU-induced thermal effect. The results indicated that, comparing with regular albumin-shelled MBs, the SPIO-albumin MBs would lead to quicker temperature elevation rate and higher peak temperature. This phenomenon could be explained by the changes in MBs’ physical and thermal properties induced by the integration of SPIOs into MB shell materials. In addition, more experimental results demonstrated that the enhancement effect on HIFU-induced temperature elevation could be further strengthened with more SPIOs combined with albumin-shell MBs. These observations suggested that more violent cavitation behaviors might be activated by ultrasound exposures with the presence of SPIOs, which in turn amplified ultrasound-stimulated thermal effect. Based on the present studies, it is reasonable to expect that, with the help of properly designed dual-modality magnetic MBs, the efficiency of HIFU-induced thermal effect could be further improved to achieve better therapeutic outcomes.

Uptake and bioreactivity of charged chitosan-coated superparamagnetic nanoparticles as promising contrast agents for magnetic resonance imaging

Bioreactivity of superparamagnetic iron oxide nanoparticles (SPION) coated with thin layers of either cationic or anionic chitosan derivatives and serving as contrast agents in magnetic resonance imaging (MRI) was studied in vivo using BALB/c mouse model. Synthesized dual-modal fluorescing SPION were tracked in time using both fluorescent imaging and MRI. Although SPION started to be excreted by kidneys relatively shortly after administration they were uptaken by liver enhancing MRI contrast even up to 7 days. Importantly, chitosan-coated SPION caused only mild activation of acute phase response not affecting biochemical parameters of blood. Liver histology indicated the presence of SPION and modest increase in the number of Kupffer cells. The overall results indicated that SPION coated with ultrathin layers of chitosan ionic derivatives can serve as T2 contrast agents for diagnosis of liver diseases or imaging of other organs assuming the dose is optimized according to the need.

Deciphering the Biochemical Pathway and Pharmacokinetic Study of Amyloid βeta-42 with Superparamagnetic Iron Oxide Nanoparticles (SPIONs) Using Systems Biology Approach.

Alzheimer's disease (AD) pathogenesis leads to the appearance of senile plaques due to the production and deposition of the β-amyloid peptide (Aβ). Superparamagnetic iron oxide nanoparticles (SPIONs) have potential role in the detection and imaging of Aβ plaques in AD. SPIONs have shown appropriate potential in the diagnosis and treatment of AD. In the present study, the pharmacokinetics of SPIONs and its effect in the biochemical pathway of AD were analyzed using collected information. During analysis, the interaction of SPIONs with amyloid beta-42 (Aβ42), a biomarker for AD progression, has been shown. Nodes represent the entities and edges represent the relation (interactions) of one node to another node. Aβ42 and their interaction with other entities making up biochemical network are involved in AD mechanism in presence of SPION. The kinetic simulation was done to investigate pharmacokinetics of SPIONs for AD, where concentration was assigned of nanoparticles and other entities were applied as a kinetic irreversible simple Michaelis-Menten or mass action kinetics. Simulation was done in presence and absence of SPIONs to investigate pharmacokinetic effect in AD and explore the mechanism of Aβ42 in presence of SPIONs. This study may lead to better understanding, which is required to target the metabolism of Aß42 peptide, a pivotal player in this pathology.

Magnetoliposomes as Potential Carriers of Doxorubicin to Tumours.

Studies on magnetoliposomes (MLUV) as potential carriers for magnetic-field-dependent drug delivery are presented. The systems were formed with hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) confined within the bilayer of the liposomes. The nanomechanical properties of bilayer lipid membranes were evaluated and related to the amount of incorporated SPIONs. It was found that the presence of SPIONs in the lipid membrane leads to overall stiffening and increases morphological inhomogeneity, facilitating rupture of the MLUV membrane in a low-frequency alternating magnetic field (AMF). To verify the findings, doxorubicin release from MLUVs in the presence and absence of an AMF was measured. Under experimental conditions, drug release proceeds through MLUV rupture induced by mechanical vibration of SPIONs rather than through localized heating in the vicinity of the SPIONs.

SPION/β-cyclodextrin core–shell nanostructures for oil spill remediation and organic pollutant removal from waste water

Water contaminated by oil, dyes and micropollutant as Bisphenol A (BPA) pose challenges to the management of water resources. In this small scale laboratory experiment we report the synthesis of superparamagnetic iron-oxide nanoparticles (SPION) and their nanocomposite with β-cyclodextrin (SPION/β-CD). Fourier transform infra red spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray (EDX), high resolution transmission electron microscopy (HRTEM), small area electron diffraction (SAED), photoluminescence (PL), UV–vis spectroscopy, Mossbauer and vibrating sample magnetometry (VSM). Visible light assisted photo-oxidation of BPA was investigated in presence of SPION and SPION/β-CD. The treatment performances were evaluated in terms of BPA degradation using UV–visible spectrophotometer, gas chromatography–mass spectrometry (GC–MS), total organic carbon analysis (TOC), chemical oxygen demand analysis (COD) and CO2 emission. 82.55% degradation was achieved through photodegradation under solar illumination. The magnetic nanocomposite was capable of scavenging oil from water as determined from oil sorption studies and magnetic separation thereof. An oil retention capacity of 7.2g/g of nanocomposite has been observed. In addition 94.22% degradation of Malachite Green dye was also achieved in a 2h sunlight driven photocatalysis process. Interestingly, the higher removal efficiency and reusability studies confirm the suitability for oil spill remediation. Magnetically recoverable, photocatalytic, bio-compatible nanocomposite of SPION and with β-cyclodextrin were prepared by the simple technique and utilized for multi pollutant removal and has a higher reusability and potential biomedical applications.

A DNA hybridization system for labeling of neural stem cells with SPIO nanoparticles for MRI monitoring post-transplantation

Neural stem cells (NSCs) demonstrate encouraging results in cell replacement therapy for neurodegenerative disorders and traumatic injury in the central nervous system. Monitor the survival and migration of transplanted cells would provide us important information concerning the performance and integration of the graft during the therapy time course. Magnetic resonance imaging (MRI) allow us to monitor the transplanted cells in a non-invasive way. The only requirement is to use an appropriate contrast agent to label the transplanted cells. Superparamagnetic iron oxide (SPIO) nanoparticles are one of the most commonly used contrast agent for MRI detection of transplanted cells. SPIO nanoparticles demonstrated to be suitable for labeling several types of cells including NSCs. However, the current methods for SPIO labeling are non-specific, depending mostly on electrostatic interactions, demanding relatively high SPIO concentration, and long incubation time, which can affect the viability of cells. In this study, we propose a specific and relatively fast method to label NSCs with SPIO nanoparticles via DNA hybridization. Two short single stranded DNAs (ssDNAs), oligo[dT]20 and oligo[dA]20 were conjugated with a lipid molecule and SPIO nanoparticle respectively. The labeling process comprises two simple steps; first the cells are modified to present oligo[dT]20 ssDNA on the cell surface, then the oligo[dA]20 ssDNA conjugated with SPIO nanoparticles are presented to the modified cells to allow the oligo[dT]20-oligo[dA]20 hybridization. The method showed to be non-toxic at concentrations up to 50 μg/mL oligo[dA]20-SPIO nanoparticles. Presence of SPIO nanoparticles at cell surface and cell cytoplasm was verified by transmission electron microscopy (TEM). SPIO labeling via DNA hybridization demonstrated to not interfere on NSCs proliferation, aggregates formation, and differentiation. NSCs labeled with SPIO nanoparticles via DNA hybridization system were successfully detected by MRI in vitro as well in vivo. Cells transplanted into the rat brain striatum could be detected by MRI scanning up to 1 month post-transplantation.

Investigation on the toxic interaction of superparamagnetic iron oxide nanoparticles with catalase

Superparamagnetic iron oxide nanoparticles (SPIONs) have been investigated for various applications in targeted drug delivery and magnetic resonance imaging. Given their clinical relevance, there is a need to understand these particles׳ potential cytotoxic effects and possible mechanisms of cytotoxicity. Using a variety of spectroscopic techniques, we investigated the interaction of SPIONs with catalase (CAT) in an aqueous environment. Catalase is an important enzyme that protects cells and tissues from oxidative damage by reactive oxygen species (ROS). Therefore, in this work, CAT served as a model protein for examining the physiological effects of SPIONs due to is function in eliminating H2O2. Synchronous fluorescence spectroscopy results showed that SPIONs have little effect on tryptophan residues in CAT. Data from circular dichroism (CD) and UV–vis spectroscopies showed that CAT α-helical content decreased from 32.4% to 29.1% in the presence of SPIONs. Moreover, a ca. 10% decrease in CAT activity was observed in the presence of SPIONs at a 20:1 particle:protein ratio. These results show that SPIONs can interact with proteins to alter both their structure and function. Further studies with CAT or other toxicologically relevant enzymes may be used for elucidating the mechanisms of SPION cytotoxicity.

Poly(ethylene glycol)-block-poly(4-vinyl pyridine) as a versatile block copolymer to prepare nanoaggregates of superparamagnetic iron oxide nanoparticles.

This work reports an efficient method for the preparation of aqueous dispersions of superparamagnetic iron oxide nanoparticles (SPIONs), involving the use of an amphiphilic block copolymer, poly(ethylene glycol)-block-poly(4-vinyl pyridine) (mPEG-b-P4VP). The iron oxide nanoparticles are easily and efficiently dispersed due to the strong direct interaction of the hydrophobic P4VP segments, through complexation with pyridine units of the copolymer. Well-defined block copolymers, having different compositions and molecular weights, were prepared by atom transfer radical polymerization (ATRP). The aqueous self-assembly behavior of each system has been compared based on the method of preparation. The results revealed that the addition of ionic species has a significant effect on the size and type of formed nanostructures, the magnitude of which is dependent on the block copolymers' molecular design. When similar self-assembly strategies were used in the presence of SPIONs, the same type of nanostructures was formed. The hybrid SPION nanoaggregates were investigated using NMR relaxometric techniques, whereby high r2/r1 relaxivity ratios were achieved, making these materials potentially efficient T2-weighted MRI contrast agents.

Magnetically Decorated Multi-Walled Carbon Nanotubes as Dual MRI and SPECT Contrast Agents.

Carbon nanotubes (CNTs) have been proposed as one of the most promising nanomaterials to be used in biomedicine for their applications in drug/gene delivery as well as biomedical imaging. The present study developed radio-labeled iron oxide decorated multi-walled CNTs (MWNT) as dual magnetic resonance (MR) and single photon emission computed tomography (SPECT) imaging agents. Hybrids containing different amounts of iron oxide were synthesized by in situ generation. Physicochemical characterisations revealed the presence of superparamagnetic iron oxide nanoparticles (SPION) granted the magnetic properties of the hybrids. Further comprehensive examinations including high resolution transmission electron microscopy (HRTEM), fast Fourier transform simulations (FFT), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) assured the conformation of prepared SPION as γ-Fe2O3. High r2 relaxivities were obtained in both phantom and in vivo MRI compared to the clinically approved SPION Endorem®. The hybrids were successfully radio-labeled with technetium-99m through a functionalized bisphosphonate and enabled SPECT/CT imaging and γ-scintigraphy to quantitatively analyze the biodistribution in mice. No abnormality was found by histological examination and the presence of SPION and MWNT were identified by Perls stain and Neutral Red stain, respectively. TEM images of liver and spleen tissues showed the co-localization of SPION and MWNT within the same intracellular vesicles, indicating the in vivo stability of the hybrids after intravenous injection. The results demonstrated the capability of the present SPION-MWNT hybrids as dual MRI and SPECT contrast agents for in vivo use.

Whole body tracking of superparamagnetic iron oxide nanoparticle-labelled cells – a rheumatoid arthritis mouse model

IntroductionThe application of mesenchymal stem cells (MSCs) in treating rheumatoid arthritis (RA) has been made possible by the immunosuppressive and differentiation abilities of these cells. A non-invasive means of assessing cell integration and bio-distribution is fundamental in evaluating the risks and success of this therapy, thereby enabling clinical translation. This paper defines the use of superparamagnetic iron oxide nanoparticles (SPIONs) in conjunction with magnetic resonance imaging (MRI) to image and track MSCs in vivo within a murine model of RA.MethodsMurine MSCs (mMSCs) were isolated, expanded and labelled with SiMAG, a commercially available particle. In vitro MRI visibility thresholds were investigated by labelling mMSCs with SiMAG with concentrations ranging from 0 to 10 μg/ml and resuspending varying cell doses (103 to 5 × 105 cells) in 2 mg/ml collagen prior to MR-imaging. Similarly, in vivo detection thresholds were identified by implanting 3 × 105 mMSCs labelled with 0 to 10 μg/ml SiMAG within the synovial cavity of a mouse and MR-imaging. Upon RA induction, 300,000 mMSCs labelled with SiMAG (10 μg/ml) were implanted via intra-articular injection and joint swelling monitored as an indication of RA development over seven days. Furthermore, the effect of SiMAG on cell viability, proliferation and differentiation was investigated.ResultsA minimum particle concentration of 1 μg/ml (300,000 cells) and cell dose of 100,000 cells (5 and 10 μg/ml) were identified as the in vitro MRI detection threshold. Cell viability, proliferation and differentiation capabilities were not affected, with labelled populations undergoing successful differentiation down osteogenic and adipogenic lineages. A significant decrease (P < 0.01) in joint swelling was measured in groups containing SiMAG-labelled and unlabelled mMSCs implying that the presence of SPIONs does not affect the immunomodulating properties of the cells. In vivo MRI scans demonstrated good contrast and the identification of SiMAG-labelled populations within the synovial joint up to 7 days post implantation. This was further confirmed using histological analysis.ConclusionsWe have been able to monitor and track the migration of stem cell populations within the rheumatic joint in a non-invasive manner. This manuscript goes further to highlight the key characteristics (biocompatible and the ability to create significant contrast at realistic doses within a clinical relevant system) demonstrated by SiMAG that should be incorporated into the design of a new clinically approved tracking agent.