Albumin-Coated Single-Core Iron Oxide Nanoparticles for Enhanced Molecular Magnetic Imaging (MRI/MPI)

Colloidal stability of magnetic iron oxide nanoparticles (MNP) in physiological environments is crucial for their (bio)medical application. MNP are potential contrast agents for different imaging modalities such as magnetic resonance imaging (MRI) and magnetic particle imaging (MPI). Applied as a hybrid method (MRI/MPI), these are valuable tools for molecular imaging. Continuously synthesized and in-situ stabilized single-core MNP were further modified by albumin coating. Synthesizing and coating of MNP were carried out in aqueous media without using any organic solvent in a simple procedure. The additional steric stabilization with the biocompatible protein, namely bovine serum albumin (BSA), led to potential contrast agents suitable for multimodal (MRI/MPI) imaging. The colloidal stability of BSA-coated MNP was investigated in different sodium chloride concentrations (50 to 150 mM) in short- and long-term incubation (from two hours to one week) using physiochemical characterization techniques such as transmission electron microscopy (TEM) for core size and differential centrifugal sedimentation (DCS) for hydrodynamic size. Magnetic characterization such as magnetic particle spectroscopy (MPS) and nuclear magnetic resonance (NMR) measurements confirmed the successful surface modification as well as exceptional colloidal stability of the relatively large single-core MNP. For comparison, two commercially available MNP systems were investigated, MNP-clusters, the former liver contrast agent (Resovist), and single-core MNP (SHP-30) manufactured by thermal decomposition. The tailored core size, colloidal stability in a physiological environment, and magnetic performance of our MNP indicate their ability to be used as molecular magnetic contrast agents for MPI and MRI.     

Magnetic Resonance Imaging of Tumor-Infiltrating Lymphocytes by Anti-CD3-Conjugated Iron Oxide Nanoparticles

Immune checkpoint blockade, considered a revolutionary approach in cancer treatment, is only effective in patients with high tumor-infiltrating lymphocytes (TILs). This work aimed to investigate the feasibility of targeted contrast agent (CA) based on dextran-coated superparamagnetic iron oxide nanoparticles (SPIONs-DEX) for TILs detection by magnetic resonance imaging (MRI) studies. To do so, we synthesized an MRI CA by conjugating SPIONs-DEX to an anti-CD3 monoclonal antibody via cyanogen bromide as a cross-linker. In vitro assessments demonstrated the higher labeling efficiency of the developed CA to CD3+ lymphocytes compared to SPIONs-DEX. In vivo MRI of a xenograft model of CD3+ lymphocytes revealed the significant signal loss after the intravenous injection of the bioconjugate by ∼34 % and 21 % in T₂*-weighted and T₂-weighted images, respectively. The histopathological evaluation of xenograft tumors confirmed the labeling of lymphocytes by the targeted CA. This approach could open up a new horizon in the non-invasive assessment of TILs to identify patients eligible for immunotherapy.     

氧化铁磁性纳米粒子的表面修饰及应用

氧化铁磁性纳米粒子因其优异的性能,广泛应用于环境分离、生物活性物质的富集和分离等领域,近年来引起了广泛的关注和研究。文章总结了氧化铁肱性纳米粒子表面修饰方法及相关应用,并对其前号进行了展望。     

Enhanced Tumor Imaging Using Glucosamine-Conjugated Polyacrylic Acid-Coated Ultrasmall Gadolinium Oxide Nanoparticles in Magnetic Resonance Imaging

Owing to a higher demand for glucosamine (GlcN) in metabolic processes in tumor cells than in normal cells (i.e., GlcN effects), tumor imaging in magnetic resonance imaging (MRI) can be highly improved using GlcN-conjugated MRI contrast agents. Here, GlcN was conjugated with polyacrylic acid (PAA)-coated ultrasmall gadolinium oxide nanoparticles (UGONs) (d_avg = 1.76 nm). Higher positive (brighter or T₁) contrast enhancements at various organs including tumor site were observed in human brain glioma (U87MG) tumor-bearing mice after the intravenous injection of GlcN-PAA-UGONs into their tail veins, compared with those obtained with PAA-UGONs as control, which were rapidly excreted through the bladder. Importantly, the contrast enhancements of the GlcN-PAA-UGONs with respect to those of the PAA-UGONs were the highest in the tumor site owing to GlcN effects. These results demonstrated that GlcN-PAA-UGONs can serve as excellent T₁ MRI contrast agents in tumor imaging via GlcN effects.     

Accumulation and Toxicity of Superparamagnetic Iron Oxide Nanoparticles in Cells and Experimental Animals

The uptake and distribution of negatively charged superparamagnetic iron oxide (Fe₃O₄) nanoparticles (SPIONs) in mouse embryonic fibroblasts NIH3T3, and magnetic resonance imaging (MRI) signal influenced by SPIONs injected into experimental animals, were visualized and investigated. Cellular uptake and distribution of the SPIONs in NIH3T3 after staining with Prussian Blue were investigated by a bright-field microscope equipped with digital color camera. SPIONs were localized in vesicles, mostly placed near the nucleus. Toxicity of SPION nanoparticles tested with cell viability assay (XTT) was estimated. The viability of NIH3T3 cells remains approximately 95% within 3–24 h of incubation, and only a slight decrease of viability was observed after 48 h of incubation. MRI studies on Wistar rats using a clinical 1.5 T MRI scanner were showing that SPIONs give a negative contrast in the MRI. The dynamic MRI measurements of the SPION clearance from the injection site shows that SPIONs slowly disappear from injection sites and only a low concentration of nanoparticles was completely eliminated within three weeks. No functionalized SPIONs accumulate in cells by endocytic mechanism, none accumulate in the nucleus, and none are toxic at a desirable concentration. Therefore, they could be used as a dual imaging agent: as contrast agents for MRI and for traditional optical biopsy by using Prussian Blue staining.     

Transferrin-Decorated Niosomes with Integrated InP/ZnS Quantum Dots and Magnetic Iron Oxide Nanoparticles: Dual Targeting and Imaging of Glioma

The development of multifunctional nanoscale systems that can mediate efficient tumor targeting, together with high cellular internalization, is crucial for the diagnosis of glioma. The combination of imaging agents into one platform provides dual imaging and allows further surface modification with targeting ligands for specific glioma detection. Herein, transferrin (Tf)-decorated niosomes with integrated magnetic iron oxide nanoparticles (MIONs) and quantum dots (QDs) were formulated (PEGNIO/QDs/MIONs/Tf) for efficient imaging of glioma, supported by magnetic and active targeting. Transmission electron microscopy confirmed the complete co-encapsulation of MIONs and QDs in the niosomes. Flow cytometry analysis demonstrated enhanced cellular uptake of the niosomal formulation by glioma cells. In vitro imaging studies showed that PEGNIO/QDs/MIONs/Tf produces an obvious negative-contrast enhancement effect on glioma cells by magnetic resonance imaging (MRI) and also improved fluorescence intensity under fluorescence microscopy. This novel platform represents the first niosome-based system which combines magnetic nanoparticles and QDs, and has application potential in dual-targeted imaging of glioma.     

Different Storage Conditions Influence Biocompatibility and Physicochemical Properties of Iron Oxide Nanoparticles

Superparamagnetic iron oxide nanoparticles (SPIONs) have attracted increasing attention in many biomedical fields. In magnetic drug targeting SPIONs are injected into a tumour supplying artery and accumulated inside the tumour with a magnet. The effectiveness of this therapy is thus dependent on magnetic properties, stability and biocompatibility of the particles. A good knowledge of the effect of storage conditions on those parameters is of utmost importance for the translation of the therapy concept into the clinic and for reproducibility in preclinical studies. Here, core shell SPIONs with a hybrid coating consisting of lauric acid and albumin were stored at different temperatures from 4 to 45 °C over twelve weeks and periodically tested for their physicochemical properties over time. Surprisingly, even at the highest storage temperature we did not observe denaturation of the protein or colloidal instability. However, the saturation magnetisation decreased by maximally 28.8% with clear correlation to time and storage temperature. Furthermore, the biocompatibility was clearly affected, as cellular uptake of the SPIONs into human T-lymphoma cells was crucially dependent on the storage conditions. Taken together, the results show that the particle properties undergo significant changes over time depending on the way they are stored.     

Collagen-Specific Molecular Magnetic Resonance Imaging of Prostate Cancer

Constant interactions between tumor cells and the extracellular matrix (ECM) influence the progression of prostate cancer (PCa). One of the key components of the ECM are collagen fibers, since they are responsible for the tissue stiffness, growth, adhesion, proliferation, migration, invasion/metastasis, cell signaling, and immune recruitment of tumor cells. To explore this molecular marker in the content of PCa, we investigated two different tumor volumes (500 mm³ and 1000 mm³) of a xenograft mouse model of PCa with molecular magnetic resonance imaging (MRI) using a collagen-specific probe. For in vivo MRI evaluation, T1-weighted sequences before and after probe administration were analyzed. No significant signal difference between the two tumor volumes could be found. However, we detected a significant difference between the signal intensity of the peripheral tumor area and the central area of the tumor, at both 500 mm³ (p < 0.01, n = 16) and at 1000 mm³ (p < 0.01, n = 16). The results of our histologic analyses confirmed the in vivo studies: There was no significant difference in the amount of collagen between the two tumor volumes (p > 0.05), but within the tumor, higher collagen expression was observed in the peripheral area compared with the central area of the tumor. Laser ablation with inductively coupled plasma mass spectrometry further confirmed these results. The 1000 mm³ tumors contained 2.8 ± 1.0% collagen and the 500 mm³ tumors contained 3.2 ± 1.2% (n = 16). There was a strong correlation between the in vivo MRI data and the ex vivo histological data (y = −0.068x + 1.1; R² = 0.74) (n = 16). The results of elemental analysis by inductively coupled plasma mass spectrometry supported the MRI data (y = 3.82x + 0.56; R² = 0.79; n = 7). MRI with the collagen-specific probe in PCa enables differentiation between different tumor areas. This may help to differentiate tumor from healthy tissue, potentially identifying tumor areas with a specific tumor biology.     

In Vitro/In Vivo Toxicity Evaluation and Quantification of Iron Oxide Nanoparticles

Increasing biomedical applications of iron oxide nanoparticles (IONPs) in academic and commercial settings have alarmed the scientific community about the safety and assessment of toxicity profiles of IONPs. The great amount of diversity found in the cytotoxic measurements of IONPs points toward the necessity of careful characterization and quantification of IONPs. The present document discusses the major developments related to in vitro and in vivo toxicity assessment of IONPs and its relationship with the physicochemical parameters of IONPs. Major discussion is included on the current spectrophotometric and imaging based techniques used for quantifying, and studying the clearance and biodistribution of IONPs. Several invasive and non-invasive quantification techniques along with the pitfalls are discussed in detail. Finally, critical guidelines are provided to optimize the design of IONPs to minimize the toxicity.     

Starch-Coated Magnetic Iron Oxide Nanoparticles for Affinity Purification of Recombinant Proteins

Starch-coated magnetic iron oxide nanoparticles have been synthesized by a simple, fast, and cost-effective co-precipitation method with cornstarch as a stabilizing agent. The structural and magnetic characteristics of the synthesized material have been studied by transmission electron microscopy, Mössbauer spectroscopy, and vibrating sample magnetometry. The nature of bonds between ferrihydrite nanoparticles and a starch shell has been examined by Fourier transform infrared spectroscopy. The data on the magnetic response of the prepared composite particles have been obtained by magnetic measurements. The determined magnetic characteristics make the synthesized material a good candidate for use in magnetic separation. Starch-coated magnetic iron oxide nanoparticles have been tested as an affinity sorbent for one-step purification of several recombinant proteins (cardiac troponin I, survivin, and melanoma inhibitory activity protein) bearing the maltose-binding protein as an auxiliary fragment. It has been shown that, due to the highly specific binding of this fragment to the starch shell, the target fusion protein is selectively immobilized on magnetic nanoparticles and eluted with the maltose solution. The excellent efficiency of column-free purification, high binding capacity of the sorbent (100–500 µg of a recombinant protein per milligram of starch-coated magnetic iron oxide nanoparticles), and reusability of the obtained material have been demonstrated.     

The Effect of Iron Oxide Magnetic Nanoparticles on Smooth Muscle Cells

Recently, magnetic nanoparticles of iron oxide (Fe₃O₄, γ-Fe₂O₃) have shown an increasing number of applications in the field of biomedicine, but some questions have been raised about the potential impact of these nanoparticles on the environment and human health. In this work, the three types of magnetic nanoparticles (DMSA-Fe₂O₃, APTS-Fe₂O₃, and GLU-Fe₂O₃) with the same crystal structure, magnetic properties, and size distribution was designed, prepared, and characterized by transmission electronic microscopy, powder X-ray diffraction, zeta potential analyzer, vibrating sample magnetometer, and Fourier transform Infrared spectroscopy. Then, we have investigated the effect of the three types of magnetic nanoparticles (DMSA-Fe₂O₃, APTS-Fe₂O₃, and GLU-Fe₂O₃) on smooth muscle cells (SMCs). Cellular uptake of nanoparticles by SMC displays the dose, the incubation time and surface property dependent patterns. Through the thin section TEM images, we observe that DMSA-Fe₂O₃ is incorporated into the lysosome of SMCs. The magnetic nanoparticles have no inflammation impact, but decrease the viability of SMCs. The other questions about metabolism and other impacts will be the next subject of further studies. Song Zhang and Xiangjian Chen contributed equally to this work.     

Magnetic Hyperthermia Nanoarchitectonics via Iron Oxide Nanoparticles Stabilised by Oleic Acid: Anti-Tumour Efficiency and Safety Evaluation in Animals with Transplanted Carcinoma

In this study, we developed iron oxide nanoparticles stabilised with oleic acid/sodium oleate that could exert therapeutic effects for curing tumours via magnetic hyperthermia. A suspension of iron oxide nanoparticles was produced and characterised. The toxicity of the synthesised composition was examined in vivo and found to be negligible. Histological examination showed a low local irritant effect and no effect on the morphology of the internal organs. The efficiency of magnetic hyperthermia for the treatment of transplanted Walker 256 carcinoma was evaluated. The tumour was infiltrated with the synthesised particles and then treated with an alternating magnetic field. The survival rate was 85% in the studied therapy group of seven animals, while in the control group (without treatment), all animals died. The physicochemical and pharmaceutical properties of the synthesised fluid and the therapeutic results, as seen in the in vivo experiments, provide insights into therapeutic hyperthermia using injected magnetite nanoparticles.     

Mutagenic Effects of Iron Oxide Nanoparticles on Biological Cells

In recent years, there has been an increased interest in the design and use of iron oxide materials with nanoscale dimensions for magnetic, catalytic, biomedical, and electronic applications. The increased manufacture and use of iron oxide nanoparticles (IONPs) in consumer products as well as industrial processes is expected to lead to the unintentional release of IONPs into the environment. The impact of IONPs on the environment and on biological species is not well understood but remains a concern due to the increased chemical reactivity of nanoparticles relative to their bulk counterparts. This review article describes the impact of IONPs on cellular genetic components. The mutagenic impact of IONPs may damage an organism’s ability to develop or reproduce. To date, there has been experimental evidence of IONPs having mutagenic interactions on human cell lines including lymphoblastoids, fibroblasts, microvascular endothelial cells, bone marrow cells, lung epithelial cells, alveolar type II like epithelial cells, bronchial fibroblasts, skin epithelial cells, hepatocytes, cerebral endothelial cells, fibrosarcoma cells, breast carcinoma cells, lung carcinoma cells, and cervix carcinoma cells. Other cell lines including the Chinese hamster ovary cells, mouse fibroblast cells, murine fibroblast cells, Mytilus galloprovincialis sperm cells, mice lung cells, murine alveolar macrophages, mice hepatic and renal tissue cells, and vero cells have also shown mutagenic effects upon exposure to IONPs. We further show the influence of IONPs on microorganisms in the presence and absence of dissolved organic carbon. The results shed light on the transformations IONPs undergo in the environment and the nature of the potential mutagenic impact on biological cells.     

纳米氧化铁的制备及其掺杂效应

纳米氧化铁作为气敏材料得到广泛重视。本文重点介绍了近年来应用比较普遍的合成纳米氧化铁的方法,如:溶胶—凝胶法、共沉淀法、水热法、水解法,并指出了各种方法的优缺点;同时,介绍了在掺杂了不同的物质后纳米氧化铁具有的独特的气敏性能;最后,对氧化铁基气敏元件的烧成工艺进行了比较。     

Heating of Foods Studied by Magnetic Resonance Imaging

MRI is the only technique that has the potential to map the temperature distribution of water in food non‐invasively in three dimensions (Nott and Hall, 1999), as well as to acquire data sensitive to the physical changes induced by heating, including delineating between frozen and thawed regions. Its practical use is illustrated here by the following set of applications: microwave heating of plastic trays containing a model gel, as well as chilled and frozen lasagne; thawing of a frozen whole chicken either at ambient temperature or by microwave heating; and by cooking of an egg in hot water. The strengths and limitations of MRI temperature mapping of real foods is discussed.     

Dual Loading of Doxorubicin and Magnetic Iron Oxide into PLA-TPGS Nanoparticles: Design,in vitro Drug Release Kinetics,and Biological Effects on Cancer Cells

The multifunctional nano drug delivery system (MNDDS) has much revolutionized in cancer treatment, aiming to eliminate many disadvantages of conventional formulations. This paper herein proposes and demonstrates MNDDS inspired by poly(lactide)-tocopheryl polyethylene glycol succinate (PLA-TPGS) copolymer co-loaded Doxorubicin and magnetic iron oxide nanoparticles (MIONs) with a 1 : 1 (w/w) optimal ratio. In vitro drug release kinetics of Doxorubicin from this nanosystem fitted best to the Weibull kinetic model and can be described by the classical Fickian diffusion mechanism under acidic pH conditions. The combination of MIONs and Doxorubicin in the PLA-TPGS copolymer has maintained the fluorescence properties of Doxorubicin and good cell penetration, especially inside the nucleus and its vicinity. Moreover, different cell cycle profiles were observed in HeLa cell lines treated with MNDDSs.     

Magnetic Iron Oxide Nanoparticles for Multimodal Imaging and Therapy of Cancer

Superparamagnetic iron oxide nanoparticles (SPION) have emerged as an MRI contrast agent for tumor imaging due to their efficacy and safety. Their utility has been proven in clinical applications with a series of marketed SPION-based contrast agents. Extensive research has been performed to study various strategies that could improve SPION by tailoring the surface chemistry and by applying additional therapeutic functionality. Research into the dual-modal contrast uses of SPION has developed because these applications can save time and effort by reducing the number of imaging sessions. In addition to multimodal strategies, efforts have been made to develop multifunctional nanoparticles that carry both diagnostic and therapeutic cargos specifically for cancer. This review provides an overview of recent advances in multimodality imaging agents and focuses on iron oxide based nanoparticles and their theranostic applications for cancer. Furthermore, we discuss the physiochemical properties and compare different synthesis methods of SPION for the development of multimodal contrast agents.     

Magnetic Particle Imaging: Current and Future Applications,Magnetic Nanoparticle Synthesis Methods and Safety Measures

Magnetic nanoparticles (MNPs) have a wide range of applications; an area of particular interest is magnetic particle imaging (MPI). MPI is an imaging modality that utilizes superparamagnetic iron oxide particles (SPIONs) as tracer particles to produce highly sensitive and specific images in a broad range of applications, including cardiovascular, neuroimaging, tumor imaging, magnetic hyperthermia and cellular tracking. While there are hurdles to overcome, including accessibility of products, and an understanding of safety and toxicity profiles, MPI has the potential to revolutionize research and clinical biomedical imaging. This review will explore a brief history of MPI, MNP synthesis methods, current and future applications, and safety concerns associated with this newly emerging imaging modality.     

Exploiting Size-Dependent Drag and Magnetic Forces for Size-Specific Separation of Magnetic Nanoparticles

Realizing the full potential of magnetic nanoparticles (MNPs) in nanomedicine requires the optimization of their physical and chemical properties. Elucidation of the effects of these properties on clinical diagnostic or therapeutic properties, however, requires the synthesis or purification of homogenous samples, which has proved to be difficult. While initial simulations indicated that size-selective separation could be achieved by flowing magnetic nanoparticles through a magnetic field, subsequent in vitro experiments were unable to reproduce the predicted results. Magnetic field-flow fractionation, however, was found to be an effective method for the separation of polydisperse suspensions of iron oxide nanoparticles with diameters greater than 20 nm. While similar methods have been used to separate magnetic nanoparticles before, no previous work has been done with magnetic nanoparticles between 20 and 200 nm. Both transmission electron microscopy (TEM) and dynamic light scattering (DLS) analysis were used to confirm the size of the MNPs. Further development of this work could lead to MNPs with the narrow size distributions necessary for their in vitro and in vivo optimization.     

Obesity-Related Neuroinflammation: Magnetic Resonance and Microscopy Imaging of the Brain

Obesity is a major risk factor of Alzheimer’s disease and related dementias. The principal feature of dementia is a loss of neurons and brain atrophy. The mechanistic links between obesity and the neurodegenerative processes of dementias are not fully understood, but recent research suggests that obesity-related systemic inflammation and subsequent neuroinflammation may be involved. Adipose tissues release multiple proinflammatory molecules (fatty acids and cytokines) that impact blood and vessel cells, inducing low-grade systemic inflammation that can transition to tissues, including the brain. Inflammation in the brain—neuroinflammation—is one of key elements of the pathobiology of neurodegenerative disorders; it is characterized by the activation of microglia, the resident immune cells in the brain, and by the structural and functional changes of other cells forming the brain parenchyma, including neurons. Such cellular changes have been shown in animal models with direct methods, such as confocal microscopy. In humans, cellular changes are less tangible, as only indirect methods such as magnetic resonance (MR) imaging are usually used. In these studies, obesity and low-grade systemic inflammation have been associated with lower volumes of the cerebral gray matter, cortex, and hippocampus, as well as altered tissue MR properties (suggesting microstructural variations in cellular and molecular composition). How these structural variations in the human brain observed using MR imaging relate to the cellular variations in the animal brain seen with microscopy is not well understood. This review describes the current understanding of neuroinflammation in the context of obesity-induced systemic inflammation, and it highlights need for the bridge between animal microscopy and human MR imaging studies.