Superparamagnetic iron oxide nanoparticles (SPIONs) have been recognized in numerous fields including nanobiotechnology, biomedical engineering, and many other fields for its inestimable ...applications. Superparamagnetic property and the smaller size of SPIONs are the major reasons for its utilization in various fields. In this review, the overall view on work done so far on SPIONS is detailed. Where, it started with different methods of synthesis of SPIONs including various types physical (such as gas-phase deposition, pulsed laser ablation, power ball milling), chemical (chemical co-precipitation, micro-emulsions, hydrothermal synthesis) and biological methods (using bacteria and plant) and are also elaborated. Its properties and characteristics are detailed. The formulation of SPIONs into drug-laden nanocarrier for exhibiting targeted drug delivery and its use in cancer treatment as hyperthermia is emphasised. Its various other applications consist of radiation therapy, environmental remediation, tissue engineering etc., which are also elaborated.
•Different method of SPIONs synthesis and characterization are explained.•The surface and magnetic property of SPIONs are described.•Applications of SPIONs including hyperthermia, cancer treatment, heavy metal removal etc are explained.
Due to their very small size, nanoparticles can interact with all cells in the central nervous system. One of the most promising nanoparticle subgroups are very small superparamagnetic iron oxide ...nanoparticles (VSOP) that are citrate coated for electrostatic stabilization. To determine their influence on murine blood-derived monocytes, which easily enter the injured central nervous system, we applied VSOP and carboxydextran-coated superparamagnetic iron oxide nanoparticles (Resovist). We assessed their impact on the viability, cytokine, and chemokine secretion, as well as iron uptake of murine blood-derived monocytes. We found that (1) the monocytes accumulated VSOP and Resovist, (2) this uptake seemed to be nanoparticle- and time-dependent, (3) the decrease of monocytes viability was treatment-related, (4) VSOP and Resovist incubation did not alter cytokine homeostasis, and (5) overall a 6-hour treatment with 0.75 mM VSOP-R1 was probably sufficient to effectively label monocytes for future experiments. Since homeostasis is not altered, it is safe to label blood-derived monocles with VSOP. VSOP labeled monocytes can be used to study injured central nervous system sites further, for example with drug-carrying VSOP.
Abstract Improving the relaxivity of magnetic resonance imaging (MRI) contrast agents is an important challenge for caner theranostic. Herein we report the design, synthesis, characterization, ...theoretical analysis and in vivo tests of a superparamagnetic polymersome as a new MRI contrast agent with extremely high T2 relaxivity (611.6 mM−1 s−1 ). First, a noncytotoxic cancer-targeting polymersome is synthesized based on a biodegradable diblock copolymer, folic acid-poly(L-glutamic acid)- block -poly( ε -caprolactone) FA-PGA- b -PCL. Then, ultra-small superparamagnetic iron oxide nanoparticles (SPIONs) are in situ generated in the hydrophilic PGA coronas of polymersomes to afford magnetic polymersomes. The in vivo MRI assay revealed prominent negative contrast enhancement of magnetic polymersomes at a very low Fe dose of 0.011 mmol/kg. Moreover, this cancer-targeting magnetic polymersome can effectively encapsulate and deliver anticancer drug to inhibit the tumor growth, demonstrating promising theranostic applications in biomedicine.
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•Superparamagnetic iron oxide nanoparticles (SPIONs) was synthesized by hydrothermal method.•SPIONs encapsulated in alginate beads (SPIONs-Alg) and both sorbents were used for arsenic ...removal.•The adsorption followed Langmuir isotherm with an adsorption capacity found to be 11.89 mg/g and 240.081 mg/g for SPIONs and SPIONs-Alg, respectively.•The thermodynamic values determined the spontaneity and endothermic nature of the As(III) adsorption process.•SPIONs-Alg after adsorption recovered using 0.1 M NaOH, and reused for five sorption– desorption process.
Superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized by the hydrothermal method and used for effective removal of arsenite, As(III), in their native and alginate beads-encapsulated (SPIONs-Alg) forms. The size of SPIONs was determined as ∼25 nm, and the structural properties of the adsorbents were validated using FTIR and XRD. The magnetization curve had zero coercivity, indicating superparamagnetism. Furthermore, the effects of pH, contact time, temperature, adsorbent dosage, and initial As(III) concentration on removal efficiency were studied. The optimum removal percentages for SPIONs and SPIONs-Alg were 99% and 90%, respectively, at pH 7, 30 °C, and 6.5 mg/L As (III) concentration.The Langmuir isotherm model (R2 ≥ 0.97 for SPIONs and R2 ≥ 0.99 for SPIONs-Alg) fitted the equilibrium data better than Freundlich. The As(III) adsorption capacity of sorbents was evaluated using the Langmuir adsorption isotherm and found to be 11.89 mg/g and 240.081 mg/g for SPIONs and SPIONs-Alg, respectively. The adsorption kinetic data for both adsorbents showed a better fit to the pseudo-second-order kinetic model (R2 ≥ 0.99). The spontaneity of the adsorption process, the endothermic nature of the sorption reaction, and the adsorbents' affinity for As(III) were determined using the negative ΔG, positive ΔH and ΔS values. SPIONs-Alg (1.5 g/l solid-to-liquid S/L ratio) could be collected easily, recovered using 0.1 M NaOH, and reused for five times (sorption ≥ 97%). The feasibility of SPIONs-Alg as a promising adsorbent for removing As(III) from wastewater is clearly validated.
Image-guided treatment of cancer enables physicians to localize and treat tumors with great precision. Here, we present in vivo results showing that an emerging imaging modality, magnetic particle ...imaging (MPI), can be combined with magnetic hyperthermia into an image-guided theranostic platform. MPI is a noninvasive 3D tomographic imaging method with high sensitivity and contrast, zero ionizing radiation, and is linearly quantitative at any depth with no view limitations. The same superparamagnetic iron oxide nanoparticle (SPIONs) tracers imaged in MPI can also be excited to generate heat for magnetic hyperthermia. In this study, we demonstrate a theranostic platform, with quantitative MPI image guidance for treatment planning and use of the MPI gradients for spatial localization of magnetic hyperthermia to arbitrarily selected regions. This addresses a key challenge of conventional magnetic hyperthermiaSPIONs delivered systemically accumulate in off-target organs (e.g., liver and spleen), and difficulty in localizing hyperthermia results in collateral heat damage to these organs. Using a MPI magnetic hyperthermia workflow, we demonstrate image-guided spatial localization of hyperthermia to the tumor while minimizing collateral damage to the nearby liver (1–2 cm distance). Localization of thermal damage and therapy was validated with luciferase activity and histological assessment. Apart from localizing thermal therapy, the technique presented here can also be extended to localize actuation of drug release and other biomechanical-based therapies. With high contrast and high sensitivity imaging combined with precise control and localization of the actuated therapy, MPI is a powerful platform for magnetic-based theranostics.
Clusters of iron oxide nanoparticles encapsulated in a pH-responsive hydrogel are synthesized and studied for their ability to alter the T2-relaxivity of protons. Encapsulation of the clusters with ...the hydrophilic coating is shown to enhance the transverse relaxation rate by up to 85% compared to clusters with no coating. With the use of pH-sensitive hydrogel, difficulties inherent in comparing particle samples are eliminated and a clear increase in relaxivity as the coating swells is demonstrated. Agreement with Monte Carlo simulations indicates that the lower diffusivity of water inside the coating and near the particle surface leads to the enhancement. This demonstration of a surface-active particle structure opens new possibilities in using similar structures for nanoparticle-based diagnostics using magnetic resonance imaging.
Nanoparticle-induced autophagy is crucial for its metabolism, cytotoxicity and therapy potency, but little is known about how the host immune system would respond to it. In this study, we ...demonstrated that two clinically used superparamagnetic iron oxide nanoparticles (SPIONs) specifically induced macrophage autophagy through activation of TLR4, followed by phosphorylation of p38 and nucleus translocation of Nrf2, leading to upregulation of p62/SQSTM1 and macrophage scavenger receptor SR-AI mRNA expression. Overexpressed p62 conjugated with LC3 to form aggresome-like induced structures (ALIS) and then fused with SPIONs containing endosomes and lysosomes to form autolysosomes for degradation of endocytosed nanoparticles. More importantly, SPIONs also could promote macrophage autophagy in mouse liver which is their imaging target. We also discovered that SPIONs could stimulate the expression of inflammatory cytokines through activation of TLR4 signaling in macrophage. In general, our findings indicate that SPIONs would interact with TLR4 on the macrophage membrane and trigger its downstream signaling pathway, independent of the classic autophagic p62 reduction pathway. The observed autophagy and induced inflammatory responses in macrophages provide unique and novel perspectives in optimizing imaging/therapy nanoparticle performance in addition to analysis by traditional biochemical evaluation methods. It also enriches our understanding of NP/macrophage interaction mechanisms in reticular endothelial system (RES) organs.
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Microencapsulation of pancreatic islets for the treatment of Type I Diabetes Mellitus (T1DM) generates a high quantity of empty microcapsules, resulting in high therapeutic graft ...volumes that can enhance the host’s immune response. We report a 3D printed microfluidic magnetic sorting device for microcapsules purification with the objective to reduce the number of empty microcapsules prior transplantation. In this study, INS1E pseudoislets were microencapsulated within alginate (A) and alginate-poly-L-lysine-alginate (APA) microcapsules and purified through the microfluidic device. APA microcapsules demonstrated higher mechanical integrity and stability than A microcapsules, showing better pseudoislets viability and biological function. Importantly, we obtained a reduction of the graft volume of 77.5% for A microcapsules and 78.6% for APA microcapsules. After subcutaneous implantation of induced diabetic Wistar rats with magnetically purified APA microencapsulated pseudoislets, blood glucose levels were restored into normoglycemia (<200 mg/dL) for almost 17 weeks. In conclusion, our described microfluidic magnetic sorting device represents a great alternative approach for the graft volume reduction of microencapsulated pseudoislets and its application in T1DM disease.
Cancer-associated fibroblasts (CAFs), are the key effector cells in pancreatic ductal adenocarcinoma (PDAC), known to induce tumor growth and progression. Pancreatic stellate cells (PSCs) are the ...precursors of CAFs in PDAC that secrete abundant extracellular matrix, growth factors and cytokines. In this study, we targeted human relaxin-2 (RLX), an endogenous hormone, to PSCs to inhibit their differentiation into CAF-like myofibroblasts. RLX significantly inhibited TGF-β induced PSCs differentiation by inhibiting pSmad2 signaling pathway. In vitro in primary human PSCs (hPSCs), treatment with RLX dose-dependently inhibited the migration, contraction, and protein expression of alpha smooth muscle actin and collagen I These data demonstrate that RLX can regulate hPSCs activation in vitro. However, RLX has several drawbacks i.e. poor pharmacokinetics and systemic vasodilation, that limits its preclinical and clinical application. Thus, we designed and successfully synthesized a nanoparticle system by chemically conjugating RLX to superparamagnetic iron oxide nanoparticle (SPION) to improve its pharmacokinetics. Interestingly, we found RLX-SPION to be more efficacious compared to free RLX in vitro. Significantly, we observed RLX-SPION retarded the tumor growth by itself and also potentiated the effect of gemcitabine in a subcutaneous co-injection (Panc1 and hPSCs) tumor model. The treatment resulted in significant inhibition in tumor growth, which was attributed to reduced collagen I (ECM), desmin (hPSC marker) and CD31 (endothelial marker) expression. In contrast, free RLX showed no significant effects. Altogether, this study presents a novel therapeutic approach against tumor stroma using RLX-SPION to achieve an effective treatment against pancreatic tumor.
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Gigantocellular reticular nucleus (GRNs) executes a vital role in locomotor recovery after spinal cord injury. However, due to its unique anatomical location deep within the brainstem, intervening in ...GRNs for spinal cord injury research is challenging. To address this problem, this study adopted an extracorporeal magnetic stimulation system to observe the effects of selective magnetic stimulation of GRNs with iron oxide nanoparticles combined treadmill training on locomotor recovery after spinal cord injury, and explored the possible mechanisms.BackgroundGigantocellular reticular nucleus (GRNs) executes a vital role in locomotor recovery after spinal cord injury. However, due to its unique anatomical location deep within the brainstem, intervening in GRNs for spinal cord injury research is challenging. To address this problem, this study adopted an extracorporeal magnetic stimulation system to observe the effects of selective magnetic stimulation of GRNs with iron oxide nanoparticles combined treadmill training on locomotor recovery after spinal cord injury, and explored the possible mechanisms.Superparamagnetic iron oxide (SPIO) nanoparticles were stereotactically injected into bilateral GRNs of mice with moderate T10 spinal cord contusion. Eight-week selective magnetic stimulation produced by extracorporeal magnetic stimulation system (MSS) combined with treadmill training was adopted for the animals from one week after surgery. Locomotor function of mice was evaluated by the Basso Mouse Scale, Grid-walking test and Treadscan analysis. Brain MRI, anterograde virus tracer and immunofluorescence staining were applied to observe the tissue compatibility of SPIO in GRNs, trace GRNs' projections and evaluate neurotransmitters' expression in spinal cord respectively. Motor-evoked potentials and H reflex were collected for assessing the integrity of cortical spinal tract and the excitation of motor neurons in anterior horn.MethodsSuperparamagnetic iron oxide (SPIO) nanoparticles were stereotactically injected into bilateral GRNs of mice with moderate T10 spinal cord contusion. Eight-week selective magnetic stimulation produced by extracorporeal magnetic stimulation system (MSS) combined with treadmill training was adopted for the animals from one week after surgery. Locomotor function of mice was evaluated by the Basso Mouse Scale, Grid-walking test and Treadscan analysis. Brain MRI, anterograde virus tracer and immunofluorescence staining were applied to observe the tissue compatibility of SPIO in GRNs, trace GRNs' projections and evaluate neurotransmitters' expression in spinal cord respectively. Motor-evoked potentials and H reflex were collected for assessing the integrity of cortical spinal tract and the excitation of motor neurons in anterior horn.(1) SPIO persisted in GRNs for a minimum of 24 weeks without inducing apoptosis of GRN cells, and degraded slowly over time. (2) MSS-enabled treadmill training dramatically improved locomotor performances of injured mice, and promoted cortico-reticulo-spinal circuit reorganization. (3) MSS-enabled treadmill training took superimposed roles through both activating GRNs to drive more projections of GRNs across lesion site and rebalancing neurotransmitters' expression in anterior horn of lumbar spinal cord.Results(1) SPIO persisted in GRNs for a minimum of 24 weeks without inducing apoptosis of GRN cells, and degraded slowly over time. (2) MSS-enabled treadmill training dramatically improved locomotor performances of injured mice, and promoted cortico-reticulo-spinal circuit reorganization. (3) MSS-enabled treadmill training took superimposed roles through both activating GRNs to drive more projections of GRNs across lesion site and rebalancing neurotransmitters' expression in anterior horn of lumbar spinal cord.These results indicate that selective MSS intervention of GRNs potentially serves as an innovative strategy to promote more spared fibers of GRNs across lesion site and rebalance neurotransmitters' expression after spinal cord injury, paving the way for the structural remodeling of neural systems collaborating with exercise training, thus ultimately contributing to the reconstruction of cortico-reticulo-spinal circuit.ConclusionThese results indicate that selective MSS intervention of GRNs potentially serves as an innovative strategy to promote more spared fibers of GRNs across lesion site and rebalance neurotransmitters' expression after spinal cord injury, paving the way for the structural remodeling of neural systems collaborating with exercise training, thus ultimately contributing to the reconstruction of cortico-reticulo-spinal circuit.
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