Small Magnetic Nanoparticles Research Articles

Co-crosslinking strategy for dual functionalization of small magnetic nanoparticles with redox probes and biological probes

Surface functionalization strategy is becoming a crucial bridge from magnetic nanoparticles (MNPs) to their broad bio-application. To realize the multiple functions of MNPs such as magnetic manipulation, target capture, and signal amplification in their use of electrochemical biosensing, co-crosslinking strategy was proposed here to construct dual-functionalized MNPs by combining ultra-sensitive redox moieties and specific biological probes. In this work, MNPs with a TEM size of 10 nm were synthesized by co-precipitation for amination and PEGylation to maintain colloid stability once dispersed in high-ionic-strength buffer (such as phosphate-buffered saline). Then, MNPs@IgG were prepared via the bis(sulfosuccinimidyl) suberate (BS3) cross-linker to conjugate these IgG onto the MNP surface, with a binding efficiency of 73%. To construct dual-functionalized MNPs, these redox probes of ferrocene-NHS (Fc) were co-crosslinked onto the MNP surface, together with IgG, by using BS3. The developed MNPs@Redox@IgG were characterized by SDS‒PAGE to identify IgG binding and by square wave voltammetry (SWV) to validate the redox signal. Additionally, the anti-CD63 antibodies were selected for the development of MNPs@anti-CD63 for use in the bio-testing of exosome sample capture. Therefore, co-crosslinking strategy paved a way to develop dual-functionalized MNPs that can be an aid of their potential utilization in diagnostic assay or electrochemical methods.Graphical

Improving tumor treatment through intratumoral injection of drug-loaded magnetic nanoparticles and low-intensity ultrasound

The intratumoral injection of therapeutic agents responsive to external stimuli has gained considerable interest in treating accessible tumors due to its biocompatibility and capacity to reduce side effects. For the first time, a novel approach is explored to investigate the feasibility of utilizing low-intensity ultrasound in combination with intratumoral injection of drug-loaded magnetic nanoparticles (MNPs) to thermal necrosis and chemotherapy with the objective of maximizing tumor damage while avoiding harm to surrounding healthy tissue. In this study, a mathematical framework is proposed based on a multi-compartment model to evaluate the effects of ultrasound transducer’s specifications, MNPs size and distribution, and drug release in response to the tumor microenvironment characteristics. The results indicate that while a higher injection rate may increase interstitial fluid pressure, it also simultaneously enhances the concentration of the therapeutic agent. Moreover, by increasing the power and frequency of the transducer, the acoustic pressure and intensity can be enhanced. This, in turn, increases the impact on accumulated MNPs, resulting in a rise in temperature and localized heat generation. Results have demonstrated that smaller MNPs have a lower capacity to generate heat compared to larger MNPs, primarily due to the impact of sound waves on them. It is worth noting that smaller MNPs have been observed to have enhanced diffusion, allowing them to effectively spread within the tumor. However, their smaller size also leads to rapid elimination from the extracellular space into the bloodstream. To summarize, this study demonstrated that the local injection of MNPs carrying drugs not only enables localized chemotherapy but also enhances the effectiveness of low-intensity ultrasound in inducing tissue thermal necrosis. The findings of this study can serve as a valuable and reliable resource for future research in this field and contribute to the development of personalized medicine.

Micromagnetic Simulations of Nanoparticles with Varying Amount of Agglomeration

AbstractMagnetic nanoparticles can be used for medical and other purposes, but can also be integrated in polymeric or other nonmagnetic matrices of diverse shapes, for example, thin‐films or fibers. In the latter case, it may be important how the magnetic nanoparticles are distributed in the matrix, a topic which is often not taken into account when such composites are investigated experimentally or theoretically. Especially for small magnetic nanoparticles of dimensions allowing coherent reversal, the magnetic properties of such polymer/magnet composites can change drastically in the case of agglomerations. Here, a method is suggested to quantify the influence of nanoparticle distributions inside nonmagnetic matrices. By changing the average distance between nanoparticles of varying diameters between highly distributed particles and perfectly packed clusters, different magnetization dynamics can be modeled by micromagnetic simulations. Here, this process is shown for various magnetic materials and diameter distributions of magnetic nano‐spheres and present corresponding micromagnetic simulation results, which underline the importance of taking into account possible magnetic agglomerations in nonmagnetic space.

One-pot synthesis of pompon-like magnetic hollow SiO2-supported Ag nanoparticles for catalytic application

In this paper, we develop a novel pompon-like magnetic hollow SiO2 -supported Ag (SiO2 @Ag) nanoparticles, in which small silver and magnetic nanoparticles were loaded on the hollow silica shell by one-pot solvothermal method. FT-IR, XRD, SEM, TEM and BET were applied to characterized the structure and morphology of the magnetic hollow SiO2 @Ag nanoparticles. The synthesized material has not only high stability and monodispersity, but also uniform surface element distribution along with good magnetic response. On this basis, we studied the catalytic performance of this pompon-like magnetic hollow SiO2 @Ag nanoparticles for the reduction of aromatic nitro compounds, and further carried out extended researches on substrates scope. Research results indicate that the pompon-like magnetic hollow SiO2 @Ag nanoparticles have broad-spectrum catalytic activity for the reduction of aromatic nitro compounds. After recycling for 8 times, it can still maintain 90% catalytic efficiency. This study provides a facile strategy for constructing hollow hierarchical structure, and expands the application of noble metal nanoparticles in organic transformation.

Combined small and large magnetic nanoparticle extraction and concentration from biofluids for non-toxic detection of biomarkers.

We propose a novel non-toxic method of diagnostic biomarker extraction and concentration from biofluids. The method is based on the usage of (1) magnetic nanoparticles of a few nanometres in size bearing molecular traps for biomarkers on their surface and (2) additional larger (several tens of nanometres) magnetic nanoparticles for catching smaller magnetic nanoparticles in a strong magnetic field gradient with their consequent concentration into the detection area. It is shown that the interference of an external permanent gradient magnetic field with the magnetic field of large magnetic nanoparticles allows one to catch small magnetic nanoparticles from their trajectories in a fluid at a distance around ten radii of the large nanoparticles. Theoretical analysis and mathematical simulation show the validity of the proposed non-toxic method for fast and robust biomarker extraction and concentration for increasing the sensitivity of biomarker detection. We believe that the results presented herein can serve as a starting point in the development of a new subclass of biosensors and a human body diagnostic approach with enhanced sensitivity and selectivity.

Simulation of magnetic nanoparticles crossing through a simplified blood-brain barrier model for Glioblastoma multiforme treatment

Background and ObjectivesGlioblastoma multiforme is considered as one of the most aggressive types of cancer, while various treatment techniques have been proposed. Magnetic nanoparticles (MNPs) loaded with drug and magnetically controlled and targeted to tissues affected by disease, is considered as a possible treatment. However, MNPs are difficult to penetrate the central nervous system and approach the unhealthy tissue, because of the blood-brain barrier (BBB). This study investigates numerically the delivery of magnetic nanoparticles through the barrier driven by normal pressure drop and external gradient magnetic fields, employing a simplified geometrical model, computational fluid dynamics and discrete element method. The goal of the study is to provide information regarding the permeability of the BBB under various conditions like the imposed forces and the shape of the domain, as a preliminary predictive tool. MethodsTo achieve that, the three-dimensional Navier-Stokes equations are solved in the margin of a blood vessel along with a discrete model for the MNPs with various acting forces. The numerical results are compared with experimental measurements showing that the model can predict acceptably the flow behavior. ResultsThe effect of nanoparticles’ size, external magnetic field and blood flow in the vessel, on the brain-barrier's permeability are investigated. Three different cases of available area among the endothelial cells per the MNPs’ size ratio are also examined, showing that the MNPs’ size and available area is not the dominant parameter affecting the permeability of the BBB. The results indicate that the applied magnetic field enhances the drug delivery into the central nervous system (CNS). When larger MNPs (∼100 nm) are exposed to an external magnetic field, the permeability can be improved up to 30%, while it is shown that smaller MNPs (∼10 nm) cannot be driven by the applied magnetic field and in this case the permeability remains relatively unchanged. Finally, the blood flow increase leads to a permeability improvement up to 15%. ConclusionsThe applied magnetic field improves up to 45% the permeability of the BBB for MNPs of 100 nm. The geometric characteristics of the endothelial cells, the nanoparticles’ size and the blood flow are not so decisive parameters for the drug delivery into the CNS, compared to the external magnetic force.

Magnetic Nanoparticles as a Tool for Remote DNA Manipulations at a Single-Molecule Level.

Remote control of cells and single molecules by magnetic nanoparticles in nonheating external magnetic fields is a perspective approach for many applications such as cancer treatment and enzyme activity regulation. However, the possibility and mechanisms of direct effects of small individual magnetic nanoparticles on such processes in magneto-mechanical experiments still remain unclear. In this work, we have shown remote-controlled mechanical dissociation of short DNA duplexes (18-60 bp) under the influence of nonheating low-frequency alternating magnetic fields using individual 11 nm magnetic nanoparticles. The developed technique allows (1) simultaneous manipulation of millions of individual DNA molecules and (2) evaluation of energies of intermolecular interactions in short DNA duplexes or in other molecules. Finally, we have shown that DNA duplexes dissociation is mediated by mechanical stress and produced by the movement of magnetic nanoparticles in magnetic fields, but not by local overheating. The presented technique opens a new avenue for high-precision manipulation of DNA and generation of biosensors for quantification of energies of intermolecular interaction.

Magnetite Nanoparticles and Spheres for Chemo- and Photothermal Therapy of Hepatocellular Carcinoma in vitro.

IntroductionWe present a multimodal nanoplatforms for the treatment of hepatocellular carcinoma (HCC) in vitro. The nanoplatforms are based on polydopamine (PDA)-coated magnetite nanoparticles (NPs) and spheres (sMAG) with PAMAM dendrimers and functionalized with NHS-PEG-Mal (N-hydroxysuccinimide–polyethylene glycol–maleimide) linker, which allows their functionalization with a folic acid derivative. The nanomaterials bearing a folic acid-targeting moiety show high efficiency in killing cancer cells in the dual chemo- and photothermal therapy (CT-PTT) of the liver cancer cells in comparison to modalities performed separately.Materials and MethodsAll materials are characterized in detail with transmission electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, zeta potential and magnetic measurements. Also, photothermal properties were determined under irradiation of nanoparticles with laser beam of 2 W/cm2. The nontoxicity of nanoparticles with doxorubicin and without was checked by WST and LIVE/DEAD assay. Those tests were also used to evaluate materials bearing folic acid and anticancer drug in combined chemo- and photothermal therapy of HCC. Further, the generation of reactive oxygen species profile was also evaluated using flow cytometry test.ResultsBoth NPs and sMAG showed high photothermal properties. Nevertheless, the higher photothermal response was found for magnetic spheres. Materials of concentration above 10 µg/mL reveal that their activity was comparable to free doxorubicin. It is worth highlighting that a functionalized magnetic sphere with DOXO more strongly affected the HepG2 cells than smaller functionalized nanoparticles with DOXO in the performed chemotherapy. This can be attributed to the larger size of particles and a different method of drug distribution. In the further stage, both materials were assessed in combined chemo- and photothermal therapy (CT-PTT) which revealed that magnetic spheres were also more effective in this modality than smaller nanoparticles.ConclusionHere, we present two types of nanomaterials (nanoparticles and spheres) based on polydopamine and PAMAM dendrimers g.5.0 functionalized with NHS-PEG-Mal linker terminated with folic acid for in vitro hepatocellular carcinoma treatment. The obtained materials can serve as efficient agents for dual chemo- and photothermal therapy of HCC. We also proved that PDA-coated magnetic spheres were more efficient in therapies based on near-infrared irradiation because determined cell viabilities for those materials are lower than for the same concentrations of nanomaterials based on small magnetic nanoparticles.

Magnetic and viscous modes for physical rotation of magnetic nanoparticles in liquid under oscillating magnetic field

The response of magnetic nanoparticles (MNPs) in a liquid to an alternating magnetic field is complicated because the rotational motions of both the magnetic moment in the MNP (internal rotation) and the MNP itself (physical rotation) affect each other. It is necessary to elucidate the mechanisms of these rotation behaviors for the success of the recent bio-applications of MNPs. However, the experimental technique for the observation of the physical rotation has been lacking. In our previous work, we demonstrated that the physical rotation of MNPs could be measured quantitatively from the absorbance change with a Faraday configuration. Then, it was revealed that the ten nm-sized maghemite MNP kept aligning to some extent with small oscillation. This behavior is consistent with the “magnetic mode” that Usov and Liubimov proposed from their numerical simulation. In the present study, we improved the apparatus to measure the induced linear dichroism with a Voigt configuration. This improvement increased the signal-to-noise ratio by about 100 times and allowed us to investigate the dependence of the physical rotation on the size of magnetite MNPs. It was shown that smaller MNPs (11 nm and 13 nm) rotated in the magnetic mode. By contrast, the rotational motion of the biggest MNP (25 nm) had different features compared to the smaller ones. These differences can be explained with “viscous mode” that Usov and Liubimov also predicted. Furthermore, we suggest a dimensionless parameter as a useful criterion for the transition of these modes.

Characterization of Binding of Magnetic Nanoparticles to Rolling Circle Amplification Products by Turn-On Magnetic Assay.

The specific binding of oligonucleotide-tagged 100 nm magnetic nanoparticles (MNPs) to rolling circle products (RCPs) is investigated using our newly developed differential homogenous magnetic assay (DHMA). The DHMA measures ac magnetic susceptibility from a test and a control samples simultaneously and eliminates magnetic background signal. Therefore, the DHMA can reveal details of binding kinetics of magnetic nanoparticles at very low concentrations of RCPs. From the analysis of the imaginary part of the DHMA signal, we find that smaller MNPs in the particle ensemble bind first to the RCPs. When the RCP concentration increases, we observe the formation of agglomerates, which leads to lower number of MNPs per RCP at higher concentrations of RCPs. The results thus indicate that a full frequency range of ac susceptibility observation is necessary to detect low concentrations of target RCPs and a long amplification time is not required as it does not significantly increase the number of MNPs per RCP. The findings are critical for understanding the underlying microscopic binding process for improving the assay performance. They furthermore suggest DHMA is a powerful technique for dynamically characterizing the binding interactions between MNPs and biomolecules in fluid volumes.

Broad-Range Magnetic Relaxation Switching Bioassays Using Click Chemistry-Mediated Assembly of Polystyrene Beads and Magnetic Nanoparticles.

Magnetic relaxation switching assays with a broad and tunable detection range can greatly improve current magnetic sensors for biochemical detections, but it remains challenging in terms of the limited detection range and low sensitivity. Herein, we report a methodology that uses click chemistry to assemble different sizes of polystyrene beads and magnetic nanoparticles to prepare versatile magnetic probes for broad-range bioassays with high sensitivity. Small magnetic nanoparticles can be controllably assembled on different sizes of polystyrene beads to form core-satellite structures, acting as broad-range probes that enable the magnetic relaxation switching assays with high sensitivity because different sizes of polystyrene beads can conjugate different numbers of small magnetic nanoparticles. On the basis of click chemistry, we assemble polystyrene beads and magnetic nanoparticles to develop a biosensing technique for analyzing three different antibiotics, with a high sensitivity and a tunable detection range from pg/mL to μg/mL.

Temperature-Responsive Magnetic Nanoparticles for Enabling Affinity Separation of Extracellular Vesicles.

Small magnetic nanoparticles that have surfaces decorated with stimuli-responsive polymers can be reversibly aggregated via a stimulus, such as temperature, to enable efficient and rapid biomarker separation. To fully realize the potential of these particles, the synthesis needs to be highly reproducible and scalable to large quantity. We have developed a new synthesis for temperature-responsive magnetic nanoparticles via an in situ co-precipitation process of Fe2+/Fe3+ salts at room temperature with poly(acrylic acid)- block-poly( N-isopropylacrylamide) diblock co-polymer template, synthesized via the reversible addition-fragmentation chain-transfer polymerization method. These particles were 56% polymer by weight with a 6.5:1 Fe/COOH ratio and demonstrated remarkable stability over a 2 month period. The hydrodynamic diameter remained constant at ∼28 nm with a consistent transition temperature of 34 °C, and the magnetic particle separation efficiency at 40 °C was ≥95% over the 2 month span. These properties were maintained for all large-scale synthesis batches. To demonstrate the practical utility of the stimuli-responsive magnetic nanoparticles, the particles were incorporated into a temperature-responsive binary reagent system and efficiently separated a model protein biomarker (mouse IgG) as well as purified extracellular vesicles derived from a human biofluid, seminal plasma. The ease of using these particles will prove beneficial for various biomedical applications.

Magnetically targeted delivery through cartilage

In this study, we have invented a method of delivering drugs deep into articular cartilage with shaped dynamic magnetic fields acting on small metallic magnetic nanoparticles with polyethylene glycol coating and average diameter of 30 nm. It was shown that transport of magnetic nanoparticles through the entire thickness of bovine articular cartilage can be controlled by a combined alternating magnetic field at 100 Hz frequency and static magnetic field of 0.8 tesla (T) generated by 1" dia. x 2" thick permanent magnet. Magnetic nanoparticles transport through bovine articular cartilage samples was investigated at various settings of magnetic field and time durations. Combined application of an alternating magnetic field and the static field gradient resulted in a nearly 50 times increase in magnetic nanoparticles transport in bovine articular cartilage tissue as compared with static field conditions. This method can be applied to locally deliver therapeutic-loaded magnetic nanoparticles deep into articular cartilage to prevent cartilage degeneration and promote cartilage repair in osteoarthritis.

Preparation and Characterisation of Highly Stable Iron Oxide Nanoparticles for Magnetic Resonance Imaging

Magnetic nanoparticles produced using aqueous coprecipitation usually exhibit wide particle size distribution. Synthesis of small and uniform magnetic nanoparticles has been the subject of extensive research over recent years. Sufficiently small superparamagnetic iron oxide nanoparticles easily permeate tissues and may enhance the contrast in magnetic resonance imaging. Furthermore, their unique small size also allows them to migrate into cells and other body compartments. To better control their synthesis, a chemical coprecipitation protocol was carefully optimised regarding the influence of the injection rate of base and incubation times. The citrate-stabilised particles were produced with a narrow average size range below 2 nm and excellent stability. The stability of nanoparticles was monitored by long-term measurement of zeta potentials and relaxivity. Biocompatibility was tested on the Caki-2 cells with good tolerance. The application of nanoparticles for magnetic resonance imaging (MRI) was then evaluated. The relaxivities (r1,r2) and r2/r1 ratio calculated from MR images of prepared phantoms indicate the nanoparticles as a promising T2-contrast probe.

Particle size- and concentration-dependent separation of magnetic nanoparticles

Small magnetic nanoparticles with a narrow size distribution are of great interest for several biomedical applications. When the size of the particles decreases, the magnetic moment of the particles decreases. This leads to a significant increase in the separation time by several orders of magnitude. Therefore, in the present study the separation processes of bionized nanoferrites (BNF) with different sizes and concentrations were investigated with the commercial Sepmag Q system. It was found that an increasing initial particle concentration leads to a reduction of the separation time for large nanoparticles due to the higher probability of building chains. Small nanoparticles showed exactly the opposite behavior with rising particle concentration up to 0.1mg(Fe)/ml. For higher iron concentrations the separation time remains constant and the measured Z-average decreases in the supernatant at same time intervals. At half separation time a high yield with decreasing hydrodynamic diameter of particles can be obtained using higher initial particle concentrations.

Facile microwave synthesis of uniform magnetic nanoparticles with minimal sample processing

We present a simple and rapid method for the synthesis of small magnetic nanoparticles (diameters in the order of 5–20nm) and narrow size distributions (CV's of 20–40%). The magnetite nanoparticles were synthesized in green solvents within minutes and the saturation magnetization of the particles was tunable by changes in the reaction conditions. We show that this particle synthesis method requires minimal processing steps and we present the successful coating of the particles with reactive bisphosphonates after synthesis without washing or centrifugation. We found minimal batch-to-batch variability and show the scalability of the particle synthesis method. We present a full characterization of the particle properties and believe that this synthesis method holds great promise for facile and rapid generation of magnetic nanoparticles with defined surface coatings for magnetic targeting applications.

Small magnetic nanoparticles decorating reduced graphene oxides to tune the electromagnetic attenuation capacity

Decorating r-GO with small NiFe2O4 nanoparticles uniformly achieves efficient and tunable microwave absorption due to the synergistic effect of dielectric and magnetic loss, originating from inducing multiple relaxations and multiple resonances, respectively.

Rapid dry-reagent immunomagnetic biosensing platform based on volumetric detection of nanoparticles on 3D structures

A dry-reagent immunomagnetic (DRIM) biosensing platform is developed for rapid high-precision quantitative analyses for in vitro diagnostics. The platform combines the advantages of immunochromatography with highly sensitive quantification of 200-nm magnetic nanoparticles (MP) from the entire volume of lateral flow membranes. The MP are registered by their non-linear magnetization at combinatorial frequencies by a portable reader that offers the detection limit of 60 zeptomoles or 0.4ng of magnetic nanolabels and extremely wide linear dynamic range of 7 orders. The efficient combination of small MP with large reaction surface of the 3D membranes has permitted the detection in human serum of as low as 25pg/ml total prostate specific antigen (PSA) during 30-min assay. The featured 3-fold signal increase per every order of concentration within 3.5 orders of magnitude allows precise analysis of antigen concentrations in a wide range. The system also provides the first tool for quantitative MP mapping along the lateral flow strip for easy development and optimization of assays. The DRIM detection can be used for simple, rapid and sensitive quantification of protein biomarkers for in vitro diagnostics both in laboratory and near-patient conditions, for food analysis, environmental monitoring, security, and safety applications.

High Temperature Magnetic Stabilization of Cobalt Nanoparticles by an Antiferromagnetic Proximity Effect.

Thermal activation tends to destroy the magnetic stability of small magnetic nanoparticles, with crucial implications for ultrahigh density recording among other applications. Here we demonstrate that low-blocking-temperature ferromagnetic (FM) Co nanoparticles (T(B)<70 K) become magnetically stable above 400 K when embedded in a high-Néel-temperature antiferromagnetic (AFM) NiO matrix. The origin of this remarkable T(B) enhancement is due to a magnetic proximity effect between a thin CoO shell (with low Néel temperature, T(N), and high anisotropy, K(AFM)) surrounding the Co nanoparticles and the NiO matrix (with high T(N) but low K(AFM)). This proximity effect yields an effective antiferromagnet with an apparent T(N) beyond that of bulk CoO, and an enhanced anisotropy compared to NiO. In turn, the Co core FM moment is stabilized against thermal fluctuations via core-shell exchange-bias coupling, leading to the observed T(B) increase. Mean-field calculations provide a semiquantitative understanding of this magnetic-proximity stabilization mechanism.

Structural characterization of copolymer embedded magnetic nanoparticles

Small magnetic nanoparticles (Fe3O4) were synthesized by co-precipitation and coated by emulsion polymerization with poly(methyl methacrylate-co-acrylic acid) (PMMA-co-AAc) to create surface functional groups that can attach drug molecules and other biomolecules. The coated and uncoated magnetite nanoparticles were stored for two years in normal closed ships and than characterized by Fourier transform infrared spectroscopy, X-ray diffraction, transmission electron microscopy, vibrating sample magnetometry, and electron paramagnetic resonance spectroscopy. The solid phase transformation of magnetite to maghemite, as well as an increase in particle size were evidenced for the uncoated nanoparticles. The coated nanoparticles preserved their magnetite structure and magnetic properties. The influences of monomers and surfactant layers on interactions between the magnetic nanoparticles evidenced that the thickness of the polymer has a significant effect on magnetic properties.