Special Issue "Magnetic Nanoparticles in Biological Applications"

A special issue of Nanomaterials (ISSN 2079-4991).

Deadline for manuscript submissions: closed (31 August 2018)

Special Issue Editor

Guest Editor
Dr. Olivier Sandre

Laboratoire de Chimie des Polymères Organiques (LCPO), Bordeaux-INP, Université de Bordeaux, CNRS, 16 avenue Pey Berland, 33607 Pessac cedex, France
Website | E-Mail
Interests: magnetic nanoparticles; superparamagnetic MRI contrast agents; magnetic hyperthermia; self-assembled copolymer micelles and vesicles (polymersomes); hybrid organic (e.g. polymer)/inorganic nanostructures; drug releasing nanoplatforms; nanomaterials study by neutron scattering

Special Issue Information

Dear Colleagues,

Developed in the 1960s initially for technological applications, stable suspensions of magnetic nanoparticles (MNPs) also called “ferrofluids”, emerged during the 1990s as building blocks for biological applications: Contrast agents for MRI, bio-assays using magnetic separation, internal heat sources for thermo-ablation of tumors, drug carriers with magnetic guiding capability or targeted drug release activated by an applied magnetic field, etc. The research on novel biocompatible MNPs is very active and multidisciplinary, as it involves chemistry for the development of the MNP core and of their coatings, but also physics for the study and optimization of their magnetic properties, pharmacology when dealing with conjugation to biological ligands, drug encapsulation, drug release, etc. From the materials point of view, the chemical composition and crystalline structure of MNP cores can be varied among several transition metals, metal alloys or metal oxides. However, most MNPs aimed to be in contact with living cells or organisms are made of magnetic iron oxides, in order to minimize the risks of toxicity that can arise with other metals (manganese, cobalt, nickel, zinc, etc.). Alternatively, mixed spinels or pristine metals can be used to optimize the magnetic moments. However, they need to be coated with biocompatible shells to avoid ion leashing, either organic or inorganic, as in the development of magnetic core-shells, or even magnetic tri-shells (e.g., ferromagnetic-antiferromagnetic junctions to create exchange bias effects). Other magnetic carriers or magnetic devices are hybrid, i.e., they combine an organic matrix and magnetic nanofillers, creating multi-functional or multimodal probes for bio-imaging. One can cite MNPs combined with liposomes, polymer micelles or vesicles, protein or mesoporous silica shells. In particular, thermosensitive matrixes (polymer chains or gels with a thermal transition, inorganic porous shells filled with wax as gate keepers, etc.) were proposed to tune the drug release kinetics by applied magnetic fields. This Special Issue focuses on all aspects of new nanomaterials using MNPs as active components for biological applications (bio-assays, diagnosis and/or imaging probes, drug delivery systems, etc.), or on the interaction of MNPs with biological media (biological fluids, cell cultures, or living organisms). Studies which shed light on the cellular uptake of MNPs and on the intra-cellular magnetic hyperthermia mechanisms are particularly welcome. Special attention will also be paid to contributions from talented early-stage researchers who are settling their original approaches or new directions in this field of research.

Dr. Olivier Sandre
Guest Editor

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Keywords

  • bio-compatible magnetic nanoparticles
  • MRI contrast agents
  • magnetic bio-assays
  • magnetic nanoparticle hyperthermia
  • magnetically guided drug carriers
  • magnetic bio-actuators
  • magnetic tumor targeting
  • magnetically activated drug release
  • magnetic structure and properties
  • magnetic metals, alloys and metal oxides
  • magnetic core-shells
  • magnetic tri-shells
  • hybrid magnetic carriers
  • magnetic medical devices
  • magnetic responsive bio-nanocomposites
  • magnetic multi-modal bio-imaging probes
  • magnetic thermo-sensitive liposomes
  • magnetic polymer micelles or vesicles
  • magnetic protein capsules
  • magnetic core-mesoporous silica shells
  • magnetic thermo-sensitive polymers or gels
  • interaction of magnetic nanoparticles with biological media
  • magnetic nanoparticle cellular uptake
  • intracellular magnetic hyperthermia
  • pre-clinical assays on magnetic hyperthermia
  • magnetic nanoparticle therapies

Published Papers (20 papers)

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Research

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Open AccessArticle Magnetic Targeting of Growth Factors Using Iron Oxide Nanoparticles
Nanomaterials 2018, 8(9), 707; https://doi.org/10.3390/nano8090707
Received: 14 August 2018 / Revised: 4 September 2018 / Accepted: 7 September 2018 / Published: 10 September 2018
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Abstract
Growth factors play an important role in nerve regeneration and repair. An attractive drug delivery strategy, termed “magnetic targeting”, aims to enhance therapeutic efficiency by directing magnetic drug carriers specifically to selected cell populations that are suitable for the nervous tissues. Here, we
[...] Read more.
Growth factors play an important role in nerve regeneration and repair. An attractive drug delivery strategy, termed “magnetic targeting”, aims to enhance therapeutic efficiency by directing magnetic drug carriers specifically to selected cell populations that are suitable for the nervous tissues. Here, we covalently conjugated nerve growth factor to iron oxide nanoparticles (NGF-MNPs) and used controlled magnetic fields to deliver the NGF–MNP complexes to target sites. In order to actuate the magnetic fields a modular magnetic device was designed and fabricated. PC12 cells that were plated homogenously in culture were differentiated selectively only in targeted sites out of the entire dish, restricted to areas above the magnetic “hot spots”. To examine the ability to guide the NGF-MNPs towards specific targets in vivo, we examined two model systems. First, we injected and directed magnetic carriers within the sciatic nerve. Second, we injected the MNPs intravenously and showed a significant accumulation of MNPs in mouse retina while using an external magnet that was placed next to one of the eyes. We propose a novel approach to deliver drugs selectively to injured sites, thus, to promote an effective repair with minimal systemic side effects, overcoming current challenges in regenerative therapeutics. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles in Biological Applications)
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Open AccessArticle Development of Magnetically Active Scaffolds for Bone Regeneration
Nanomaterials 2018, 8(9), 678; https://doi.org/10.3390/nano8090678
Received: 1 August 2018 / Revised: 27 August 2018 / Accepted: 28 August 2018 / Published: 30 August 2018
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Abstract
This work reports on the synthesis, with the thermally induced phase separation (TIPS) technique, of poly (l-lactide) (PLLA) scaffolds containing Fe-doped hydroxyapatite (FeHA) particles for bone regeneration. Magnetization curves and X-ray diffraction indicate two magnetic particle phases: FeHA and magnetite Fe
[...] Read more.
This work reports on the synthesis, with the thermally induced phase separation (TIPS) technique, of poly (l-lactide) (PLLA) scaffolds containing Fe-doped hydroxyapatite (FeHA) particles for bone regeneration. Magnetization curves and X-ray diffraction indicate two magnetic particle phases: FeHA and magnetite Fe3O4. Magnetic nanoparticles (MNPs) are approximately 30 ± 5 nm in width and 125 ± 25 nm in length, and show typical ferromagnetic properties, including coercivity and rapid saturation magnetization. Scanning electron microscopy (SEM) images of the magnetic scaffolds reveal their complex morphology changes with MNP concentration. Similarly, at compositions of approximately 20% MNPs, the phase separation changes, passing from solid–liquid to liquid–liquid as revealed by the hill-like structures, with low peaks that give the walls in the SEM images a surface pattern of micro-ruggedness typical of nucleation mechanisms and growth. In vitro degradation experiments, carried out for more than 28 weeks, demonstrated that the MNPs delay the scaffold degradation process. Cytotoxicity is appreciated for FeHA content above 20%. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles in Biological Applications)
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Open AccessArticle Kinetics of Aggregation and Magnetic Separation of Multicore Iron Oxide Nanoparticles: Effect of the Grafted Layer Thickness
Nanomaterials 2018, 8(8), 623; https://doi.org/10.3390/nano8080623
Received: 5 July 2018 / Revised: 26 July 2018 / Accepted: 12 August 2018 / Published: 17 August 2018
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Abstract
In this work, we have studied field-induced aggregation and magnetic separation—realized in a microfluidic channel equipped with a single magnetizable micropillar—of multicore iron oxide nanoparticles (IONPs) also called “nanoflowers” of an average size of 27 ± 4 nm and covered by either a
[...] Read more.
In this work, we have studied field-induced aggregation and magnetic separation—realized in a microfluidic channel equipped with a single magnetizable micropillar—of multicore iron oxide nanoparticles (IONPs) also called “nanoflowers” of an average size of 27 ± 4 nm and covered by either a citrate or polyethylene (PEG) monolayer having a thickness of 0.2–1 nm and 3.4–7.8 nm, respectively. The thickness of the adsorbed molecular layer is shown to strongly affect the magnetic dipolar coupling parameter because thicker molecular layers result in larger separation distances between nanoparticle metal oxide multicores thus decreasing dipolar magnetic forces between them. This simple geometrical constraint effect leads to the following important features related to the aggregation and magnetic separation processes: (a) Thinner citrate layer on the IONP surface promotes faster and stronger field-induced aggregation resulting in longer and thicker bulk needle-like aggregates as compared to those obtained with a thicker PEG layer; (b) A stronger aggregation of citrated IONPs leads to an enhanced retention capacity of these IONPs by a magnetized micropillar during magnetic separation. However, the capture efficiency Λ at the beginning of the magnetic separation seems to be almost independent of the adsorbed layer thickness. This is explained by the fact that only a small portion of nanoparticles composes bulk aggregates, while the main part of nanoparticles forms chains whose capture efficiency is independent of the adsorbed layer thickness but depends solely on the Mason number Ma. More precisely, the capture efficiency shows a power law trend Λ M a n , with n ≈ 1.4–1.7 at 300 < Ma < 104, in agreement with a new theoretical model. Besides these fundamental issues, the current work shows that the multicore IONPs with a size of about 30 nm have a good potential for use in biomedical sensor applications where an efficient low-field magnetic separation is required. In these applications, the nanoparticle surface design should be carried out in a close feedback with the magnetic separation study in order to find a compromise between biological functionalities of the adsorbed molecular layer and magnetic separation efficiency. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles in Biological Applications)
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Open AccessArticle Distribution of Paramagnetic Fe2O3/SiO2–Core/Shell Nanoparticles in the Rat Lung Studied by Time-of-Flight Secondary Ion Mass Spectrometry: No Indication for Rapid Lipid Adsorption
Nanomaterials 2018, 8(8), 571; https://doi.org/10.3390/nano8080571
Received: 10 July 2018 / Revised: 23 July 2018 / Accepted: 24 July 2018 / Published: 26 July 2018
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Abstract
Amorphous silica nanoparticles comprise a class of widely used industrial nanomaterials, which may elicit acute inflammation in the lung. These materials have a large specific surface to which components of the pulmonary micro-milieu can bind. To conduct appropriate binding studies, paramagnetic Fe2
[...] Read more.
Amorphous silica nanoparticles comprise a class of widely used industrial nanomaterials, which may elicit acute inflammation in the lung. These materials have a large specific surface to which components of the pulmonary micro-milieu can bind. To conduct appropriate binding studies, paramagnetic Fe2O3/SiO2 core/shell nanoparticles (Fe-Si-NP) may be used as an easy-to-isolate silica surrogate, if several prerequisites are fulfilled. To this end, we investigated the distribution of Fe, Si, protein and phosphatidylcholine (PC) by Time-of-Flight secondary ion mass spectrometry (ToF-SIMS) in cryo-sections from the rat lungs to which Fe-Si-NP had been administered for 30 min. Regions-of-interest were identified and analyzed with incident light and enhanced dark-field microscopy (DFM). Fe-Si-NP particles (primary particle size by electron microscopy: 10–20 nm; aggregate size by tracking analysis: 190 ± 20 nm) and agglomerates thereof were mainly attached to alveolar walls and only marginally internalized by cells such as alveolar macrophages. The localization of Fe-Si-NP by DFM was confirmed by ToF-SIMS signals from both, Fe and Si ions. With respect to an optimized signal-to-noise ratio, Fe+, Si+, CH4N+ and the PC head group (C5H15NO4P+) were the most versatile ions to detect iron, silica, protein, and PC, respectively. Largely congruent Fe+ and Si+ signals demonstrated that the silica coating of Fe-Si-NP remained stable under the conditions of the lung. PC, as a major lipid of the pulmonary surfactant, was colocalized with the protein signal alongside alveolar septa, but was not detected on Fe-Si-NP, suggesting that silica nanoparticles do not adsorb lipids of the lung surfactant under native conditions. The study shows that ToF-SIMS is a valuable technique with adequate spatial resolution to analyze nanoparticles together with organic molecules in the lung. The paramagnetic Fe-Si-NP appear well suited to study the binding of proteins to silica nanomaterials in the lung. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles in Biological Applications)
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Open AccessArticle Combined Treatments of Magnetic Intra-Lysosomal Hyperthermia with Doxorubicin Promotes Synergistic Anti-Tumoral Activity
Nanomaterials 2018, 8(7), 468; https://doi.org/10.3390/nano8070468
Received: 30 May 2018 / Revised: 14 June 2018 / Accepted: 19 June 2018 / Published: 27 June 2018
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Abstract
Doxorubicin is a cytotoxic drug used for the treatment of many cancer types. However, its significant dose-related adverse effects including cardiotoxicity may hamper its efficiency. Moreover, the multidrug resistance that appears during treatments limits anti-cancer therapies. Hyperthermia has been introduced as an adjuvant
[...] Read more.
Doxorubicin is a cytotoxic drug used for the treatment of many cancer types. However, its significant dose-related adverse effects including cardiotoxicity may hamper its efficiency. Moreover, the multidrug resistance that appears during treatments limits anti-cancer therapies. Hyperthermia has been introduced as an adjuvant anti-cancer therapy and presents promising opportunities especially in combination with chemotherapy. However, hyperthermia methods including standard magnetic hyperthermia do not discriminate between the target and the surrounding normal tissues and can lead to side effects. In this context, a Magnetic Intra-Lysosomal Hyperthermia (MILH) approach, which occurs without perceptible temperature rise, has been developed. We previously showed that minute amounts of iron oxide magnetic nanoparticles targeting the gastrin receptor (CCK2R) are internalized by cancer cells through a CCK2R-dependent physiological process, accumulated into their lysosomes and kill cancer cells upon high frequency alternating magnetic field (AMF) application through lysosomal cell death. Here, we show that the combination of MILH with doxorubicin increases the efficiency of the eradication of endocrine tumor cells with synergism. We also demonstrate that these two treatments activate two different cell death pathways that are respectively dependent on Caspase-1 and Caspase-3 activation. These findings will result in the development of new anti-tumoral, intra-lysosomal-thermo/chemotherapy with better curative effects than chemotherapy alone and that are devoid of adverse effects linked to standard hyperthermia approaches. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles in Biological Applications)
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Open AccessArticle Role of Mn2+ Doping in the Preparation of Core-Shell Structured Fe3O4@upconversion Nanoparticles and Their Applications in T1/T2-Weighted Magnetic Resonance Imaging, Upconversion Luminescent Imaging and Near-Infrared Activated Photodynamic Therapy
Nanomaterials 2018, 8(7), 466; https://doi.org/10.3390/nano8070466
Received: 25 May 2018 / Revised: 21 June 2018 / Accepted: 22 June 2018 / Published: 26 June 2018
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Abstract
Core-shell (C/S) structured upconversion coated Fe3O4 nanoparticles (NPs) are of great interest due to their potential as magnetic resonance imaging (MRI) and upconversion luminescent (UCL) imaging agents, as well as near-infrared activated photodynamic therapy (PDT) platforms. When C/S structured Fe
[...] Read more.
Core-shell (C/S) structured upconversion coated Fe3O4 nanoparticles (NPs) are of great interest due to their potential as magnetic resonance imaging (MRI) and upconversion luminescent (UCL) imaging agents, as well as near-infrared activated photodynamic therapy (PDT) platforms. When C/S structured Fe3O4@Mn2+-doped NaYF4:Yb/Er NPs were prepared previously, well-defined C/S-NPs could not be formed without the doping of Mn2+ during synthesis. Here, the role of Mn2+ doping on the synthesis of core-shell structured magnetic-upconversion nanoparticles (MUCNPs) is investigated in detail. Core-shell-shell nanoparticles (C/S/S-MUCNPs) with Fe3O4 as the core, an inert layer of Mn2+-doped NaYF4 and an outer shell consisting of Mn2+-doped NaYF4:Yb/Er were prepared. To further develop C/S/S-MUCNPs applications in the biological field, amphiphilic poly(maleic anhydride-alt-1-octadecene) (C18PMH) modified with amine functionalized methoxy poly(ethylene glycol) (C18PMH-mPEG) was used as a capping ligand to modify the surface of C/S/S-MUCNPs to improve biocompatibility. UCL imaging, T1-weighted MRI ascribed to the Mn2+ ions and T2-weighted MRI ascribed to the Fe3O4 core of C/S/S-MUCNPs were then evaluated. Finally, chlorine e6 (Ce6) was loaded on the C/S/S-MUCNPs and the PDT performance of these NPs was explored. Mn2+ doping is an effective method to control the formation of core-shell structured MUCNPs, which would be potential candidate as multifunctional nanoprobes for future T1/T2-weighted MR/UCL imaging and PDT platforms. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles in Biological Applications)
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Open AccessArticle Iron Oxide Colloidal Nanoclusters as Theranostic Vehicles and Their Interactions at the Cellular Level
Nanomaterials 2018, 8(5), 315; https://doi.org/10.3390/nano8050315
Received: 16 April 2018 / Revised: 4 May 2018 / Accepted: 4 May 2018 / Published: 9 May 2018
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Abstract
Advances in surfactant-assisted chemical approaches have led the way for the exploitation of nanoscale inorganic particles in medical diagnosis and treatment. In this field, magnetically-driven multimodal nanotools that perform both detection and therapy, well-designed in size, shape and composition, are highly advantageous. Such
[...] Read more.
Advances in surfactant-assisted chemical approaches have led the way for the exploitation of nanoscale inorganic particles in medical diagnosis and treatment. In this field, magnetically-driven multimodal nanotools that perform both detection and therapy, well-designed in size, shape and composition, are highly advantageous. Such a theranostic material—which entails the controlled assembly of smaller (maghemite) nanocrystals in a secondary motif that is highly dispersible in aqueous media—is discussed here. These surface functionalized, pomegranate-like ferrimagnetic nanoclusters (40–85 nm) are made of nanocrystal subunits that show a remarkable magnetic resonance imaging contrast efficiency, which is better than that of the superparamagnetic contrast agent Endorem©. Going beyond this attribute and with their demonstrated low cytotoxicity in hand, we examine the critical interaction of such nanoprobes with cells at different physiological environments. The time-dependent in vivo scintigraphic imaging of mice experimental models, combined with a biodistribution study, revealed the accumulation of nanoclusters in the spleen and liver. Moreover, the in vitro proliferation of spleen cells and cytokine production witnessed a size-selective regulation of immune system cells, inferring that smaller clusters induce mainly inflammatory activities, while larger ones induce anti-inflammatory actions. The preliminary findings corroborate that the modular chemistry of magnetic iron oxide nanoclusters stimulates unexplored pathways that could be driven to alter their function in favor of healthcare. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles in Biological Applications)
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Open AccessArticle Bare Iron Oxide Nanoparticles for Magnetic Harvesting of Microalgae: From Interaction Behavior to Process Realization
Nanomaterials 2018, 8(5), 292; https://doi.org/10.3390/nano8050292
Received: 5 March 2018 / Revised: 18 April 2018 / Accepted: 27 April 2018 / Published: 1 May 2018
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Abstract
Microalgae continue to gain in importance as a bioresource, while their harvesting remains a major challenge at the moment. This study presents findings on microalgae separation using low-cost, easy-to-process bare iron oxide nanoparticles with the additional contribution of the upscaling demonstration of this
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Microalgae continue to gain in importance as a bioresource, while their harvesting remains a major challenge at the moment. This study presents findings on microalgae separation using low-cost, easy-to-process bare iron oxide nanoparticles with the additional contribution of the upscaling demonstration of this simple, adhesion-based process. The high affinity of the cell wall for the inorganic surface enables harvesting efficiencies greater than 95% for Scenedesmus ovalternus and Chlorella vulgaris. Successful separation is possible in a broad range of environmental conditions and primarily depends on the nanoparticle-to-microalgae mass ratio, whereas the effect of pH and ionic strength are less significant when the mass ratio is chosen properly. The weakening of ionic concentration profiles at the interphase due to the successive addition of deionized water leads the microalgae to detach from the nanoparticles. The process works efficiently at the liter scale, enabling complete separation of the microalgae from their medium and the separate recovery of all materials (algae, salts, and nanoparticles). The current lack of profitable harvesting processes for microalgae demands innovative approaches to encourage further development. This application of magnetic nanoparticles is an example of the prospects that nanobiotechnology offers for biomass exploitation. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles in Biological Applications)
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Open AccessCommunication Can Pulsed Electromagnetic Fields Trigger On-Demand Drug Release from High-Tm Magnetoliposomes?
Nanomaterials 2018, 8(4), 196; https://doi.org/10.3390/nano8040196
Received: 19 February 2018 / Revised: 22 March 2018 / Accepted: 23 March 2018 / Published: 27 March 2018
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Abstract
Recently, magnetic nanoparticles (MNPs) have been used to trigger drug release from magnetoliposomes through a magneto-nanomechanical approach, where the mechanical actuation of the MNPs is used to enhance the membrane permeability. This result can be effectively achieved with low intensity non-thermal alternating magnetic
[...] Read more.
Recently, magnetic nanoparticles (MNPs) have been used to trigger drug release from magnetoliposomes through a magneto-nanomechanical approach, where the mechanical actuation of the MNPs is used to enhance the membrane permeability. This result can be effectively achieved with low intensity non-thermal alternating magnetic field (AMF), which, however, found rare clinic application. Therefore, a different modality of generating non-thermal magnetic fields has now been investigated. Specifically, the ability of the intermittent signals generated by non-thermal pulsed electromagnetic fields (PEMFS) were used to verify if, once applied to high-transition temperature magnetoliposomes (high-Tm MLs), they could be able to efficiently trigger the release of a hydrophilic model drug. To this end, hydrophilic MNPs were combined with hydrogenated soybean phosphatidylcholine and cholesterol to design high-Tm MLs. The release of a dye was evaluated under the effect of PEMFs for different times. The MNPs motions produced by PEMF could effectively increase the bilayer permeability, without affecting the liposomes integrity and resulted in nearly 20% of release after 3 h exposure. Therefore, the current contribution provides an exciting proof-of-concept for the ability of PEMFS to trigger drug release, considering that PEMFS find already application in therapy due to their anti-inflammatory effects. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles in Biological Applications)
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Open AccessArticle Optimization of Iron Oxide Tracer Synthesis for Magnetic Particle Imaging
Nanomaterials 2018, 8(4), 180; https://doi.org/10.3390/nano8040180
Received: 23 February 2018 / Revised: 17 March 2018 / Accepted: 19 March 2018 / Published: 21 March 2018
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Abstract
The optimization of iron oxide nanoparticles as tracers for magnetic particle imaging (MPI) alongside the development of data acquisition equipment and image reconstruction techniques is crucial for the required improvements in image resolution and sensitivity of MPI scanners. We present a large-scale water-based
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The optimization of iron oxide nanoparticles as tracers for magnetic particle imaging (MPI) alongside the development of data acquisition equipment and image reconstruction techniques is crucial for the required improvements in image resolution and sensitivity of MPI scanners. We present a large-scale water-based synthesis of multicore superparamagnetic iron oxide nanoparticles stabilized with dextran (MC-SPIONs). We also demonstrate the preparation of single core superparamagnetic iron oxide nanoparticles in organic media, subsequently coated with a poly(ethylene glycol) gallic acid polymer and phase transferred to water (SC-SPIONs). Our aim was to obtain long-term stable particles in aqueous media with high MPI performance. We found that the amplitude of the third harmonic measured by magnetic particle spectroscopy (MPS) at 10 mT is 2.3- and 5.8-fold higher than Resovist for the MC-SPIONs and SC-SPIONs, respectively, revealing excellent MPI potential as compared to other reported MPI tracer particle preparations. We show that the reconstructed MPI images of phantoms using optimized multicore and specifically single-core particles are superior to that of commercially available Resovist, which we utilize as a reference standard, as predicted by MPS. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles in Biological Applications)
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Open AccessArticle Magnetic Nanoparticles Interact and Pass an In Vitro Co-Culture Blood-Placenta Barrier Model
Nanomaterials 2018, 8(2), 108; https://doi.org/10.3390/nano8020108
Received: 14 December 2017 / Revised: 8 February 2018 / Accepted: 9 February 2018 / Published: 14 February 2018
PDF Full-text (1662 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Magnetic nanoparticles are interesting tools for biomedicine. Before application, critical prerequisites have to be fulfilled. An important issue is the contact and interaction with biological barriers such as the blood-placenta barrier. In order to study these processes in detail, suitable in vitro models
[...] Read more.
Magnetic nanoparticles are interesting tools for biomedicine. Before application, critical prerequisites have to be fulfilled. An important issue is the contact and interaction with biological barriers such as the blood-placenta barrier. In order to study these processes in detail, suitable in vitro models are needed. For that purpose a blood-placenta barrier model based on the trophoblast-like cell line BeWo and primary placenta-derived pericytes was established. This model was characterized by molecular permeability, transepithelial electrical resistance and cell-cell-contact markers. Superparamagnetic iron oxide nanoparticles (SPIONs) with cationic, anionic or neutral surface charge were applied. The localization of the nanoparticles within the cells was illustrated by histochemistry. The time-dependent passage of the nanoparticles through the BeWo/pericyte barrier was measured by magnetic particle spectroscopy and atomic absorption spectroscopy. Cationically coated SPIONs exhibited the most extensive interaction with the BeWo cells and remained primarily in the BeWo/pericyte cell layer. In contrast, SPIONs with neutral and anionic surface charge were able to pass the cell layer to a higher extent and could be detected beyond the barrier after 24 h. This study showed that the mode of SPION interaction with and passage through the in vitro blood-placenta barrier model depends on the surface charge and the duration of treatment. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles in Biological Applications)
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Open AccessCommunication Improved Anticancer Effect of Magnetite Nanocomposite Formulation of GALLIC Acid (Fe3O4-PEG-GA) Against Lung, Breast and Colon Cancer Cells
Nanomaterials 2018, 8(2), 83; https://doi.org/10.3390/nano8020083
Received: 6 December 2017 / Revised: 24 January 2018 / Accepted: 25 January 2018 / Published: 2 February 2018
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Abstract
Lung cancer, breast cancer and colorectal cancer are the most prevalent fatal types of cancers globally. Gallic acid (3,4,5-trihydroxybenzoic acid) is a bioactive compound found in plants and foods, such as white tea, witch hazel and it has been reported to possess anticancer,
[...] Read more.
Lung cancer, breast cancer and colorectal cancer are the most prevalent fatal types of cancers globally. Gallic acid (3,4,5-trihydroxybenzoic acid) is a bioactive compound found in plants and foods, such as white tea, witch hazel and it has been reported to possess anticancer, antioxidant and anti-inflammatory properties. In this study we have redesigned our previously reported anticancer nanocomposite formulation with improved drug loading based on iron oxide magnetite nanoparticles coated with polyethylene glycol and loaded with anticancer drug gallic acid (Fe3O4-PEG-GA). The in vitro release profile and percentage drug loading were found to be better than our previously reported formulation. The anticancer activity of pure gallic acid (GA), empty carrier (Fe3O4-PEG) nanocarrier and of anticancer nanocomposite (Fe3O4-PEG-GA) were screened against human lung cancer cells (A549), human breast cancer cells (MCF-7), human colon cancer cells (HT-29) and normal fibroblast cells (3T3) after incubation of 24, 48 and 72 h using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT assay. The designed formulation (Fe3O4-PEG-GA) showed better anticancer activity than free gallic acid (GA). The results of the in vitro studies are highly encouraging to conduct the in vivo studies. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles in Biological Applications)
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Open AccessArticle A Novel Magnetic Actuation Scheme to Disaggregate Nanoparticles and Enhance Passage across the Blood–Brain Barrier
Nanomaterials 2018, 8(1), 3; https://doi.org/10.3390/nano8010003
Received: 16 November 2017 / Revised: 14 December 2017 / Accepted: 16 December 2017 / Published: 22 December 2017
Cited by 1 | PDF Full-text (2372 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The blood–brain barrier (BBB) hinders drug delivery to the brain. Despite various efforts to develop preprogramed actuation schemes for magnetic drug delivery, the unmodeled aggregation phenomenon limits drug delivery performance. This paper proposes a novel scheme with an aggregation model for a feed-forward
[...] Read more.
The blood–brain barrier (BBB) hinders drug delivery to the brain. Despite various efforts to develop preprogramed actuation schemes for magnetic drug delivery, the unmodeled aggregation phenomenon limits drug delivery performance. This paper proposes a novel scheme with an aggregation model for a feed-forward magnetic actuation design. A simulation platform for aggregated particle delivery is developed and an actuation scheme is proposed to deliver aggregated magnetic nanoparticles (MNPs) using a discontinuous asymmetrical magnetic actuation. The experimental results with a Y-shaped channel indicated the success of the proposed scheme in steering and disaggregation. The delivery performance of the developed scheme was examined using a realistic, three-dimensional (3D) vessel simulation. Furthermore, the proposed scheme enhanced the transport and uptake of MNPs across the BBB in mice. The scheme presented here facilitates the passage of particles across the BBB to the brain using an electromagnetic actuation scheme. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles in Biological Applications)
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Open AccessArticle Influence of Sterilization and Preservation Procedures on the Integrity of Serum Protein-Coated Magnetic Nanoparticles
Nanomaterials 2017, 7(12), 453; https://doi.org/10.3390/nano7120453
Received: 30 October 2017 / Revised: 8 December 2017 / Accepted: 12 December 2017 / Published: 15 December 2017
PDF Full-text (2919 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Protein-coated magnetic nanoparticles are promising candidates for various medical applications. Prior to their application into a biological system, one has to guarantee that the particle dispersions are free from pathogens or any other microbiologic contamination. Furthermore, to find entrance into clinical routine, the
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Protein-coated magnetic nanoparticles are promising candidates for various medical applications. Prior to their application into a biological system, one has to guarantee that the particle dispersions are free from pathogens or any other microbiologic contamination. Furthermore, to find entrance into clinical routine, the nanoparticle dispersions have to be storable for several months. In this study, we tested several procedures for sterilization and preservation of nanoparticle containing liquids on their influence on the integrity of the protein coating on the surface of these particles. For this, samples were treated by freezing, autoclaving, lyophilization, and ultraviolet (UV) irradiation, and characterized by means of dynamic light scattering, determination of surface potential, and gel electrophoresis afterwards. We found that the UV sterilization followed by lyophilization under the addition of polyethylene glycol are the most promising procedures for the preparation of sterilized long-term durable protein-coated magnetic nanoparticles. Ongoing work is focused on the optimization of used protocols for UV sterilization and lyophilization for further improvement of the storage time. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles in Biological Applications)
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Open AccessArticle Surface Functionalization of Iron Oxide Nanoparticles with Gallic Acid as Potential Antioxidant and Antimicrobial Agents
Nanomaterials 2017, 7(10), 306; https://doi.org/10.3390/nano7100306
Received: 5 August 2017 / Revised: 28 August 2017 / Accepted: 30 August 2017 / Published: 5 October 2017
Cited by 3 | PDF Full-text (867 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this research, we report the size-controlled synthesis and surface-functionalization of magnetite with the natural antioxidant gallic acid (GA) as a ligand, using in situ and post-synthesis methods. GA functionalization provided narrow size distribution, with an average particle size of 5 and 8
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In this research, we report the size-controlled synthesis and surface-functionalization of magnetite with the natural antioxidant gallic acid (GA) as a ligand, using in situ and post-synthesis methods. GA functionalization provided narrow size distribution, with an average particle size of 5 and 8 nm for in situ synthesis of gallic acid functionalized magnetite IONP@GA1 and IONP@GA2, respectively, which are ultra-small particles as compared to unfunctionalized magnetite (IONP) and post functionalized magnetite IONP@GA3 with average size of 10 and 11 nm respectively. All the IONPs@GA samples were found hydrophilic with stable aggregation state. Prior to commencement of experimental lab work, PASS software was used to predict the biological activities of GA and it is found that experimental antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and antimicrobial studies using well diffusion method are in good agreement with the simulated results. Furthermore, the half maximal inhibitory concentration (IC50) values of DPPH antioxidant assay revealed a 2–4 fold decrease as compared to unfunctionalized IONP. In addition to antioxidant activity, all the three IONP@GA proved outstanding antimicrobial activity while testing on different bacterial and fungal strains. The results collectively indicate the successful fabrication of novel antioxidant, antimicrobial IONP@GA composite, which are magnetically separable, efficient, and low cost, with potential applications in polymers, cosmetics, and biomedical and food industries. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles in Biological Applications)
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Open AccessArticle Tuning Properties of Iron Oxide Nanoparticles in Aqueous Synthesis without Ligands to Improve MRI Relaxivity and SAR
Nanomaterials 2017, 7(8), 225; https://doi.org/10.3390/nano7080225
Received: 19 July 2017 / Revised: 1 August 2017 / Accepted: 2 August 2017 / Published: 18 August 2017
Cited by 7 | PDF Full-text (3140 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Aqueous synthesis without ligands of iron oxide nanoparticles (IONPs) with exceptional properties still remains an open issue, because of the challenge to control simultaneously numerous properties of the IONPs in these rigorous settings. To solve this, it is necessary to correlate the synthesis
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Aqueous synthesis without ligands of iron oxide nanoparticles (IONPs) with exceptional properties still remains an open issue, because of the challenge to control simultaneously numerous properties of the IONPs in these rigorous settings. To solve this, it is necessary to correlate the synthesis process with their properties, but this correlation is until now not well understood. Here, we study and correlate the structure, crystallinity, morphology, as well as magnetic, relaxometric and heating properties of IONPs obtained for different durations of the hydrothermal treatment that correspond to the different growth stages of IONPs upon initial co-precipitation in aqueous environment without ligands. We find that their properties were different for IONPs with comparable diameters. Specifically, by controlling the growth of IONPs from primary to secondary particles firstly by colloidal and then also by magnetic interactions, we control their crystallinity from monocrystalline to polycrystalline IONPs, respectively. Surface energy minimization in the aqueous environment along with low temperature treatment is used to favor nearly defect-free IONPs featuring superior properties, such as high saturation magnetization, magnetic volume, surface crystallinity, the transversal magnetic resonance imaging (MRI) relaxivity (up to r2 = 1189 mM−1·s−1 and r2/r1 = 195) and specific absorption rate, SAR (up to 1225.1 W·gFe−1). Full article
(This article belongs to the Special Issue Magnetic Nanoparticles in Biological Applications)
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Review

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Open AccessReview Magnetic Nanoparticles Applications for Amyloidosis Study and Detection: A Review
Nanomaterials 2018, 8(9), 740; https://doi.org/10.3390/nano8090740
Received: 31 August 2018 / Revised: 14 September 2018 / Accepted: 16 September 2018 / Published: 18 September 2018
PDF Full-text (4234 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Magnetic nanoparticles (MNPs) have great potential in biomedical and clinical applications because of their many unique properties. This contribution provides an overview of the MNPs mainly used in the field of amyloid diseases. The first part discusses their use in understanding the amyloid
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Magnetic nanoparticles (MNPs) have great potential in biomedical and clinical applications because of their many unique properties. This contribution provides an overview of the MNPs mainly used in the field of amyloid diseases. The first part discusses their use in understanding the amyloid mechanisms of fibrillation, with emphasis on their ability to control aggregation of amyloidogenic proteins. The second part deals with the functionalization by various moieties of numerous MNPs’ surfaces (molecules, peptides, antibody fragments, or whole antibodies of MNPs) for the detection and the quantification of amyloid aggregates. The last part of this review focuses on the use of MNPs for magnetic-resonance-based amyloid imaging in biomedical fields, with particular attention to the application of gadolinium-based paramagnetic nanoparticles (AGuIX), which have been recently developed. Biocompatible AGuIX nanoparticles show favorable characteristics for in vivo use, such as nanometric and straightforward functionalization. Their properties have enabled their application in MRI. Here, we report that AGuIX nanoparticles grafted with the Pittsburgh compound B can actively target amyloid aggregates in the brain, beyond the blood–brain barrier, and remain the first step in observing amyloid plaques in a mouse model of Alzheimer’s disease. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles in Biological Applications)
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Open AccessReview Magnetic Hyperthermia and Radiation Therapy: Radiobiological Principles and Current Practice
Nanomaterials 2018, 8(6), 401; https://doi.org/10.3390/nano8060401
Received: 29 April 2018 / Revised: 30 May 2018 / Accepted: 1 June 2018 / Published: 3 June 2018
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Abstract
Hyperthermia, though by itself generally non-curative for cancer, can significantly increase the efficacy of radiation therapy, as demonstrated by in vitro, in vivo, and clinical results. Its limited use in the clinic is mainly due to various practical implementation difficulties, the most important
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Hyperthermia, though by itself generally non-curative for cancer, can significantly increase the efficacy of radiation therapy, as demonstrated by in vitro, in vivo, and clinical results. Its limited use in the clinic is mainly due to various practical implementation difficulties, the most important being how to adequately heat the tumor, especially deep-seated ones. In this work, we first review the effects of hyperthermia on tissue, the limitations of radiation therapy and the radiobiological rationale for combining the two treatment modalities. Subsequently, we review the theory and evidence for magnetic hyperthermia that is based on magnetic nanoparticles, its advantages compared with other methods of hyperthermia, and how it can be used to overcome the problems associated with traditional techniques of hyperthermia. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles in Biological Applications)
Open AccessReview Recommendations for In Vitro and In Vivo Testing of Magnetic Nanoparticle Hyperthermia Combined with Radiation Therapy
Nanomaterials 2018, 8(5), 306; https://doi.org/10.3390/nano8050306
Received: 19 March 2018 / Revised: 22 April 2018 / Accepted: 29 April 2018 / Published: 6 May 2018
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Abstract
Magnetic nanoparticle (MNP)-mediated hyperthermia (MH) coupled with radiation therapy (RT) is a novel approach that has the potential to overcome various practical difficulties encountered in cancer treatment. In this work, we present recommendations for the in vitro and in vivo testing and application
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Magnetic nanoparticle (MNP)-mediated hyperthermia (MH) coupled with radiation therapy (RT) is a novel approach that has the potential to overcome various practical difficulties encountered in cancer treatment. In this work, we present recommendations for the in vitro and in vivo testing and application of the two treatment techniques. These recommendations were developed by the members of Working Group 3 of COST Action TD 1402: Multifunctional Nanoparticles for Magnetic Hyperthermia and Indirect Radiation Therapy (“Radiomag”). The purpose of the recommendations is not to provide definitive answers and directions but, rather, to outline those tests and considerations that a researcher must address in order to perform in vitro and in vivo studies. The recommendations are divided into 5 parts: (a) in vitro evaluation of MNPs; (b) in vitro evaluation of MNP-cell interactions; (c) in vivo evaluation of the MNPs; (d) MH combined with RT; and (e) pharmacokinetic studies of MNPs. Synthesis and characterization of the MNPs, as well as RT protocols, are beyond the scope of this work. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles in Biological Applications)
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Open AccessReview Iron Oxide and Gold Based Magneto-Plasmonic Nanostructures for Medical Applications: A Review
Nanomaterials 2018, 8(3), 149; https://doi.org/10.3390/nano8030149
Received: 22 December 2017 / Revised: 9 February 2018 / Accepted: 26 February 2018 / Published: 7 March 2018
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Abstract
Iron oxide and gold-based magneto-plasmonic nanostructures exhibit remarkable optical and superparamagnetic properties originating from their two different components. As a consequence, they have improved and broadened the application potential of nanomaterials in medicine. They can be used as multifunctional nanoprobes for magneto-plasmonic heating
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Iron oxide and gold-based magneto-plasmonic nanostructures exhibit remarkable optical and superparamagnetic properties originating from their two different components. As a consequence, they have improved and broadened the application potential of nanomaterials in medicine. They can be used as multifunctional nanoprobes for magneto-plasmonic heating as well as for magnetic and optical imaging. They can also be used for magnetically assisted optical biosensing, to detect extreme traces of targeted bioanalytes. This review introduces the previous work on magneto-plasmonic hetero-nanostructures including: (i) their synthesis from simple “one-step” to complex “multi-step” routes, including seed-mediated and non-seed-mediated methods; and (ii) the characterization of their multifunctional features, with a special emphasis on the relationships between their synthesis conditions, their structures and their properties. It also focuses on the most important progress made with regard to their use in nanomedicine, keeping in mind the same aim, the correlation between their morphology—namely spherical and non-spherical, core-satellite and core-shell, and the desired applications. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles in Biological Applications)
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