Iron Oxide-based Nanoparticles Research Articles

Dextran-coated iron oxide nanoparticle for delivery of miR-29a to breast cancer cell line

In the last years, miRNAs have been associated with molecular pathways of cancer and other diseases. The change of expression level of miRNA has an inhibitory role in tumorigenesis. Nevertheless, the poor bioavailability of miRNA due to the rapid enzymatic degradation is a critical handicap in cancer therapy. In this study, we designed dextran-coated iron oxide-based nanoparticle for the delivery of miR-29a to breast cancer cells and analyzed its therapeutic efficacy in vitro. Results indicated that the presence of dextran-coated magnetic nanoparticles, loaded with miR29a, enhanced the selective delivery of miR-29a. Further, miR-29a complex nanoparticles caused down-regulation of anti-apoptotic genes. These results pave the way for further investigations into the possible use of miR-29a complex magnetic nanoparticles for breast cancer therapy.

Applications of Iron Oxide-Based Magnetic Nanoparticles in the Diagnosis and Treatment of Bacterial Infections.

Diseases caused by bacterial infections, especially drug-resistant bacteria have seriously threatened human health throughout the world. It has been predicted that antimicrobial resistance alone will cause 10 million deaths per year and that early diagnosis and therapy will efficiently decrease the mortality rate caused by bacterial infections. Considering this severity, it is urgent to develop effective methods for the early detection, prevention and treatment of these infections. Until now, numerous efforts based on nanoparticles have been made to detect and kill pathogenic bacteria. Iron oxide-based magnetic nanoparticles (MNPs), as potential platforms for bacteria detection and therapy, have drawn great attention owing to their magnetic property. These MNPs have also been broadly used as bioimaging contrast agents and drug delivery and magnetic hyperthermia agents to diagnose and treat bacterial infections. This review therefore overviews the recent progress on MNPs for bacterial detection and therapy, including bacterial separation and enrichment in vitro, bacterial infection imaging in vivo, and their therapeutic activities on pathogenic bacteria. Furthermore, some bacterial-specific targeting agents, used to selectively target the pathogenic bacteria, are also introduced. In addition, the challenges and future perspective of MNPs for bacterial diagnosis and therapy are given at the end of this review. It is expected that this review will provide a better understanding toward the applications of MNPs in the detection and therapy of bacterial infections.

Inhibition of inflammatory response in human keratinocytes by magnetic nanoparticles functionalized with PBP10 peptide derived from the PIP2-binding site of human plasma gelsolin

BackgroundHuman plasma gelsolin (pGSN) is a multifunctional actin-binding protein involved in a variety of biological processes, including neutralization of pro-inflammatory molecules such as lipopolysaccharide (LPS) and lipoteichoic acid (LTA) and modulation of host inflammatory response. It was found that PBP10, a synthetic rhodamine B-conjugated peptide, based on the phosphoinositide-binding site of pGSN, exerts bactericidal activity against Gram-positive and Gram-negative bacteria, interacts specifically with LPS and LTA, and limits microbial-induced inflammatory effects. The therapeutic efficiency of PBP10 when immobilized on the surface of iron oxide-based magnetic nanoparticles was not evaluated, to date.ResultsUsing the human keratinocyte cell line HaCaT stimulated by bacterially-derived LPS and LTA as an in vitro model of bacterial infection, we examined the anti-inflammatory effects of nanosystems consisting of iron oxide-based magnetic nanoparticles with aminosilane (MNP@NH2) or gold shells (MNP@Au) functionalized by a set of peptides, derived from the phosphatidylinositol 4,5-bisphosphate (PIP2)-binding site of the human plasma protein gelsolin, which also binds LPS and LTA. Our results indicate that these nanosystems can kill both Gram-positive and Gram-negative bacteria and limit the production of inflammatory mediators, including nitric oxide (NO), reactive oxygen species (ROS), and interleukin-8 (IL-8) in the response to heat-killed microbes or extracted bacterial cell wall components. The nanoparticles possess the potential to improve therapeutic efficacy and are characterized by lower toxicity and improved hemocompatibility when compared to free peptides. Atomic force microscopy (AFM) showed that these PBP10-based nanosystems prevented changes in nanomechanical properties of cells that were otherwise stimulated by LPS.ConclusionsNeutralization of endotoxemia-mediated cellular effects by gelsolin-derived peptides and PBP10-containing nanosystems might be considered as potent therapeutic agents in the improved therapy of bacterial infections and microbial-induced inflammation.

Cold atmospheric plasma and iron oxide-based magnetic nanoparticles for synergetic lung cancer therapy

Cold atmospheric plasma (CAP) is an emerging biomedical technique that shows great potential for cancer treatment. On the other hand, magnetic nanoparticles open up a wide field of possible applications in medicine. Here we seek to develop a novel dual cancer therapeutic method by integrating promising CAP and iron oxide-based magnetic nanoparticles (MNPs), and evaluate its underlying mechanism for targeted lung cancer treatment. For this purpose, the synergistic effects of CAP and iron oxide-based MNPs on cellular bioactivity, epidermal growth factor receptor (EGFR) expression, and EGFR downstream signaling pathways were investigated. Results showed that the effectiveness of CAP and iron oxide-based MNPs for synergistic strongly killed activity against lung cancer cells, and significantly inhibited cell proliferation via reduction of viability and induction of apoptosis. Importantly, CAP combining with iron oxide-based MNPs induced EGFR downregulation while CAP inhibited lung cancer cells via depressing pERK and pAKT. Translation of these findings to an in vivo setting demonstrates that CAP combining iron oxide-based MNPs is effective at preventing xenograft tumors. Thus, the integration of CAP and iron oxide-based MNPs provides a promising tool for the development of a new cancer treatment strategy.

Bioconjugation and Fluorescence Labeling of Iron Oxide Nanoparticles Grafted with Bromomaleimide-Terminal Polymers.

Iron oxide nanoparticles have been widely applied in biomedical applications for their unique physical properties. Despite the relatively mature synthetic approaches for iron oxide nanoparticles, surface modification strategies for obtaining particles with satisfactory biofunctionality are still urgently needed to meet the challenge of nanomedicine. Herein, we report a surface modification and biofunctionalization strategy for iron oxide-based magnetic nanoparticles based on a dibromomaleimide (DBM)-terminated polymer with brushed polyethylene glycol (PEG) chains. PEG acrylate and phosphonate monomers, serving as antibiofouling and surface anchoring compartments for iron oxide nanoparticles, were incorporated utilizing a novel DBM containing reversible addition-fragmentation chain transfer (RAFT) agent. The particles prepared through this new surface architecture possessed high colloidal stability in a physiological buffer and the capacity of covalent conjugation with biomolecules for targeting. Cell tracking of the molecular probes was achieved concomitantly by exploiting DBM conjugation-induced fluorescence of the nanoparticles.

Anisometric Iron Oxide-Based Nanoparticles and Sols Based on Them: Preparation and Properties

We have synthesized magnetic powders of the magnetite-maghemite series by the chemical reaction of the FeSO4 iron salt and the natural arabinogalactan polysaccharide. These particles with a high magnetization value (∼ 300 Gs) represent a mixture of spherical particles and nanorods. Particles of a spherical shape (diameter of ∼ 5–6 nm) show a superparamagnetic behavior at room temperature, while rods with a diameter of ∼ 5 nm and a length of 30 nm are magnetic. We have prepared sol samples based on the nanoparticle aqueous solution of arabinogalactan. Our results on the magnetism of the circular dichroism (MCD) on sol are consistent with the of Mossbauer spectroscopy data.

Specific T cell induction using iron oxide based nanoparticles as subunit vaccine adjuvant

ABSTRACTMetal-based nanoparticles (NPs) stimulate innate immunity; however, they have never been demonstrated to be capable of aiding the generation of specific cellular immune responses. Therefore, our objective was to evaluate whether iron oxide-based NPs have adjuvant properties in generating cellular Th1, Th17 and TCD8 (Tc1) immune responses. For this purpose, a fusion protein (CMX) composed of Mycobacterium tuberculosis antigens was used as a subunit vaccine. Citrate-coated MnFe2O4 NPs were synthesized by co-precipitation and evaluated by transmission electron microscopy. The vaccine was formulated by homogenizing NPs with the recombinant protein, and protein corona formation was determined by dynamic light scattering and field-emission scanning electron microscopy. The vaccine was evaluated for the best immunization route and strategy using subcutaneous and intranasal routes with 21-day intervals between immunizations. When administered subcutaneously, the vaccine generated specific CD4+IFN-γ+ (Th1) and CD8+IFN-γ+ responses. Intranasal vaccination induced specific Th1, Th17 (CD4+IL-17+) and Tc1 responses, mainly in the lungs. Finally, a mixed vaccination strategy (2 subcutaneous injections followed by one intranasal vaccination) induced a Th1 (in the spleen and lungs) and splenic Tc1 response but was not capable of inducing a Th17 response in the lungs. This study shows for the first time a subunit vaccine with iron oxide based NPs as an adjuvant that generated cellular immune responses (Th1, Th17 and TCD8), thereby exhibiting good adjuvant qualities. Additionally, the immune response generated by the subcutaneous administration of the vaccine diminished the bacterial load of Mtb challenged animals, showing the potential for further improvement as a vaccine against tuberculosis.

Polyacrylic acid-coated iron oxide magnetic nanoparticles: The polymer molecular weight influence

Magnetic nanoparticles (MNPs), in particular, magnetic iron oxide-based nanoparticles were found to be useful as catalysts and as devices for data storage, environmental remediation and several biomedical applications, due to their excellent properties, such as biocompatibility and high magnetic moment. Polyacrylic acid (PAA) is a weak polyelectrolyte that can be used to stabilize the MNPs. To the best of our knowledge, the influence of PAA molecular weight and PAA concentration over the magnetic and structural properties of iron oxide nanoparticles has not been previously reported. The aim of this paper is to describe the differences evidenced in the properties of different magnetic materials by using PAA for iron oxides stabilization by one-pot coprecipitation synthesis. Iron oxide-based magnetic nanoparticles stabilized by polyacrylic acid (PAA) polymers were efficiently prepared and exhaustively characterized. The influence on the employment of two different low PAA molecular weights, Mw 1800 g/mol and 5000 g/mol, in three different iron salts: PAA ratios was analyzed. In summary, the main results showed that: for a certain PAA reactor feed higher oligomer quantities are present in MNPs as higher is the involved molecular weight of the polymeric chain; when molecular weight raises the contribution of loops and tails also does it, allowing having higher polymer contents. For both PAA’s Mw employed as the adsorbed PAA increases particles hydrodynamic diameters decreases, and their distribution becomes narrower; the PAA adsorbs onto iron oxides by chemisorption (the most probable interaction is the bidentate bridging). For the studied cases z potential values depend much more on the PAA’s quantity adsorbed onto the iron oxides than on the PAA’s Mw. MNPs are superparamagnetic and choosing the right shape of particle distribution is not central for getting estimates of the magnetization saturation, the average particle diameter and its standard deviation, while better fits are found with Normal and Log-Normal particle size distributions.

Physicochemical properties and in vitro cytotoxicity of iron oxide-based nanoparticles modified with antiangiogenic and antitumor peptide A7R

Superparamagnetic iron oxide-based nanoparticles (SPIONs) are promising carriers as targeted drug delivery vehicles, because they can be guided to their target with the help of an external magnetic field. Functionalization of nanoparticles’ surface with molecules, which bind with high affinity to receptors on target tissue significantly facilitates delivery of coated nanoparticles to their targeted site. Here, we demonstrate conjugation of an antiangiogenic and antitumor peptide ATWLPPR (A7R) to SPIONs modified with sebacic acid (SPIONs-SA). Successful conjugation was confirmed by various analytical techniques (FTIR, SERS, SEM-EDS, TEM, TGA). Cell cytotoxicity studies, against two cell lines (HUVEC and MDA-MB-231) indicated that SPIONs modified with A7R reduced HUVEC cell viability at concentrations higher than 0.01 mg Fe/mL, in comparison to cells that were exposed to either the nanoparticles modified with sebacic acid or A7R peptide solely, what might be partially caused by a process of internalization.

Iron Oxide Nanoradiomaterials: Combining Nanoscale Properties with Radioisotopes for Enhanced Molecular Imaging.

The combination of the size-dependent properties of nanomaterials with radioisotopes is emerging as a novel tool for molecular imaging. There are numerous examples already showing how the controlled synthesis of nanoparticles and the incorporation of a radioisotope in the nanostructure offer new features beyond the simple addition of different components. Among the different nanomaterials, iron oxide-based nanoparticles are the most used in imaging because of their versatility. In this review, we will study the different radioisotopes for biomedical imaging, how to incorporate them within the nanoparticles, and what applications they can be used for. Our focus is directed towards what is new in this field, what the nanoparticles can offer to the field of nuclear imaging, and the radioisotopes hybridized with nanomaterials for use in molecular imaging.

Exchange Bias Effects in Iron Oxide-Based Nanoparticle Systems.

The exploration of exchange bias (EB) on the nanoscale provides a novel approach to improving the anisotropic properties of magnetic nanoparticles for prospective applications in nanospintronics and nanomedicine. However, the physical origin of EB is not fully understood. Recent advances in chemical synthesis provide a unique opportunity to explore EB in a variety of iron oxide-based nanostructures ranging from core/shell to hollow and hybrid composite nanoparticles. Experimental and atomistic Monte Carlo studies have shed light on the roles of interface and surface spins in these nanosystems. This review paper aims to provide a thorough understanding of the EB and related phenomena in iron oxide-based nanoparticle systems, knowledge of which is essential to tune the anisotropic magnetic properties of exchange-coupled nanoparticle systems for potential applications.

Magnetic properties of iron oxide-based nanoparticles: Study using Mössbauer spectroscopy with a high velocity resolution and magnetization measurements

We review the results of the study of magnetite, maghemite and nickel ferrite nanoparticles (NPs), applying for magnetic fluids, using Mössbauer spectroscopy with a high velocity resolution and magnetization measurements. The Mössbauer spectra of these NPs were fitted using a large number of magnetic sextets reflecting NPs complicity. The presence of polar molecules at the magnetite surface in magnetic fluid increases the NPs magnetic moment and the median hyperfine magnetic field. However, surface coating of maghemite NPs with dimeracptosuccinic acid decreases the median hyperfine magnetic field. An example of nickel ferrite NPs demonstrated a new physical model based on distribution of Ni2+ in the local microenvironment of Fe3+ which can explain a large number of magnetic sextets in the Mössbauer spectra measured with a high velocity resolution.

Magnetocontrollability of Fe7C3@C superparamagnetic nanoparticles in living cells.

BackgroundA new type of superparamagnetic nanoparticles with chemical formula Fe7C3@C (MNPs) showed higher value of magnetization compared to traditionally used iron oxide-based nanoparticles as was shown in our previous studies. The in vitro biocompatibility tests demonstrated that the MNPs display high efficiency of cellular uptake and do not affect cyto-physiological parameters of cultured cells. These MNPs display effective magnetocontrollability in homogeneous liquids but their behavior in cytoplasm of living cells under the effect of magnetic field was not carefully analyzed yet.ResultsIn this work we investigated the magnetocontrollability of MNPs interacting with living cells in permanent magnetic field. It has been shown that cells were capable of capturing MNPs by upper part of the cell membrane, and from the surface of the cultivation substrate during motion process. Immunofluorescence studies using intracellular endosomal membrane marker showed that MNP agglomerates can be either located in endosomes or lying free in the cytoplasm. When attached cells were exposed to a magnetic field up to 0.15 T, the MNPs acquired magnetic moment and the displacement of incorporated MNP agglomerates in the direction of the magnet was observed. Weakly attached or non-attached cells, such as cells in mitosis or after cytoskeleton damaging treatments moved towards the magnet. During long time cultivation of cells with MNPs in a magnetic field gradual clearing of cells from MNPs was observed. It was the result of removing MNPs from the surface of the cell agglomerates discarded in the process of exocytosis.ConclusionsOur data allow us to conclude for the first time that the magnetic properties of the MNPs are sufficient for successful manipulation with MNP agglomerates both at the intracellular level, and within the whole cell. The structure of the outer shells of the MNPs allows firmly associate different types of biological molecules with them. This creates prospects for the use of such complexes for targeted delivery and selective removal of selected biological molecules from living cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-016-0219-4) contains supplementary material, which is available to authorized users.

Design of iron oxide-based nanoparticles for MRI and magnetic hyperthermia.

Iron oxide nanoparticles are widely used for biological applications thanks to their outstanding balance between magnetic properties, surface-to-volume ratio suitable for efficient functionalization and proven biocompatibility. Their development for MRI or magnetic particle hyperthermia concentrates much of the attention as these nanomaterials are already used within the health system as contrast agents and heating mediators. As such, the constant improvement and development for better and more reliable materials is of key importance. On this basis, this review aims to cover the rational design of iron oxide nanoparticles to be used as MRI contrast agents or heating mediators in magnetic hyperthermia, and reviews the state of the art of their use as nanomedicine tools.

Hydrophilic iron oxide nanoparticles probe the organization of biomimetic layers: electrochemical and spectroscopic evidence

Biomimetic films of mixed lipids were challenged with 15nm hydrophilic, superparamagnetic, iron oxide-based magnetic nanoparticles (SPIONs). These nanoparticles were stabilized with citrate and were allowed to interact with lipidic Langmuir films spread on an aqueous subphase or with Langmuir-Blodgett (LB) monolayers and Langmuir-Blodgett/Langmuir Schaeffer (LB/LS) bilayers transferred onto solid supports. The goal of this work is to evaluate the nature of SPIONs-cellular membrane interactions, and to attempt to separate the physicochemical aspects of such interactions from the biological ones. The ultimate utility of SPIONs lies in their potential for medical applications, such as targeted drug delivery, magnetic resonance imaging or theranostics in general. Systematic experimental studies were carried out with complementary techniques, such as LB and LB/LS film deposition, Brewster angle microscopy (BAM) imaging of the films, electrochemical impedance spectroscopy, surface enhanced resonance Raman spectroscopy SE(R)RS and fluorescence lifetime and anisotropy decay imaging (FLIM and FADI) techniques. The data presented here indicate that SPIONs have a measurable effect on the phase behavior of mixed monolayers, altering the organization of monolayer and bilayer films, and inducing changes in the formation of domains.

New era of treatment and evaluation of traumatic brain injury and spinal cord injury.

Traumatic brain injury (TBI) and spinal cord injury (SCI) are leading causes of death and disability worldwide (Center for Disease Control, 2006). Both injuries are induced by external traumatic event and likely happen together. After the primary traumatic incident, the secondary injury, including ischemic, inflammatory, metabolic and biochemical cascades, is likely more devastating (Blumbergs, 1997). To date, all clinical trials have failed to cure TBI and SCI, due to the heterogeneous and complex nature of injury pathophysiology (Saatman et al., 2008). There is no single technique that can completely assess the pathophysiological profile of TBI or SCI. Similarly, we cannot expect one single drug to cure this complex phenomenon either. Thus novel approaches are needed for therapeutic development and evaluation. In this special issue, a collection of five succinct reviews summarized the state of the art research from injury detection to novel treatment. This collection also serves as the Proceedings of 2015 Chinese Neurotrauma Scholars Association (CNSA) Symposium held in July, 2014 in San Francisco, CA, USA. The authors are invited speakers at the symposium and also leaders in their respective fields. Instead of giving lengthy systematic reviews, the papers meant to summarize the current cutting edge development and offer meaningful insights of the field to layman readers.

Controlled Magnetic Properties of Iron Oxide-Based Nanoparticles for Smart Therapy

Controlled Magnetic Properties of Iron Oxide-Based Nanoparticles for Smart Therapy

Developing novel strategies for the functionalization of core–shell magnetic nanoparticles with folic acid derivatives

In this work, we explore the development of new synthetic strategies leading to the formation of folic acid di-ester functionalized iron oxide-based magnetic nanoparticles. For this, initially, folic acid di-ester was converted into an acrylamide monomer through amidation of the primary amine site. Interestingly, esterification with a different acid chloride molecule carrying a long alkyl chain terminated with an azide group resulted into amidation of the secondary amine site. In a different set of experiments, magnetite nanoparticles decorated with a polymerization initiator, an acrylamide monomer, or a terminal alkyne group, were prepared. These folic acid and magnetic nanoparticles building blocks could then be combined in different ways to give rise to the targeted materials. In the first scheme, folic acid-based monomer could be polymerized through the initiating sites located at the surface of the magnetic nanoparticles. Alternatively, a random copolymerization between the folic acid-based monomer was carried out with the monomeric sites stabilizing the nanoparticles. Finally, the alkyne functionalities of the nanoparticles were coupled with the azide moieties of the folic acid derivatives. Thus, three different synthetic strategies were established for the formation of folic acid di-ester functionalized core–shell magnetic nanoparticles.

High Specific Absorption Rate and Transverse Relaxivity Effects in Manganese Ferrite Nanoparticles Obtained by an Electrochemical Route

Superparamagnetic iron oxide-based nanoparticles (SPIONS) have attracted an enormous amount of attention for their potential use in biomedical applications, due to their good biocompatibility and low toxicity. The current study considers citric acid-conjugated manganese ferrite and its synergy to be used in MRI and in hyperthermia treatment, thus showing theragnostic applications. High colloidal stability was obtained with this functionalization. SPIONS with superparamagnetic behavior of crystal sizes of approximately 20 nm were obtained via an electrochemical synthesis method. One of the highest specific absorption rate (SAR) values was achieved in this work (1661 W g–1), under a magnetic field of 30 mT at 717 kHz frequency, compared with other magnetic ferrites in the literature. These nanoparticles dissipate heat through Néel relaxation and, together with the high SAR value obtained, indicate an excellent material for hyperthermia treatment of cancer. In addition, these nanoparticles exhibit transverse relaxivity behavior, with an r2 value of 394 mM–1 s–1, i.e., at least two times higher than the value of a commercial magnetic contrast agent based on iron oxides. Finally, no toxicity effects of these nanoparticles are evidenced; as a result, these nanoparticles are appropriate for in vivo application.

Highly magnetic Fe2O3 nanoparticles synthesized by laser pyrolysis used for biological and heat transfer applications

γFe2O3-based nanoparticles were synthesized by laser pyrolysis using various optimized Fe(CO)5, O2 and C2H4 flow ratios in the reactive mixture, and different laser power values. Depending on particular conditions, two different iron oxide-based nanoparticles (MNPs) were synthesized, with a hydrophilic or hydrophobic behavior, both presenting a high magnetization saturation (around 70emu/g). TEM, EDX, XRD and magnetic analyses were performed for a comprehensive characterization. The raw powders were successfully dispersed in aqueous media using l-DOPA as stabilizing agent. Dispersed samples, with or without stabilization agents, have been tested and DLS measurements proved their good stability, with the hydrodynamic diameter varying between 70 and 150nm when the stabilizing agent was used. Thermal conductivity and viscosity tests on l-DOPA-functionalized MNPs suspensions reveal the increasing (up to 40%) of their thermal conductivity, accompanied by a viscosity increase of only 5%, validating them as thermal transfer fluids. Water-based nanoparticle dispersions and also those stabilized with l-DOPA proved a good biocompatibility, as demonstrated by a preliminary in vitro study on mouse primary leukocytes and human breast carcinoma cell line MCF-7; although ingested by the investigated cells, MNPs do not decrease cellular viability and proliferation.