Use Of Superparamagnetic Iron Oxide Nanoparticles Research Articles

Evolution and refinement of magnetically guided sentinel lymph node detection in breast cancer: meta-analysis.

Superparamagnetic iron oxide nanoparticles (SPIO) have been used as a tracer for sentinel lymph node (SLN) localization in breast cancer, demonstrating comparable performance to the combination of radioisotope (RI) and blue dye (BD). A systematic literature search and meta-analysis with subgroup and meta-regression analysis were undertaken to update the available evidence, assess technique evolution, and define knowledge gaps. Recommendations were made using the GRADE approach. In 20 comparative studies, the detection rate was 97.5 per cent for SPIO and 96.5 per cent for RI ± BD (risk ratio 1.006, 95 per cent c.i. 0.992 to 1.019; P = 0.376, high-certainty evidence). Neoadjuvant therapy, injection site, injection volume or nodal metastasis burden did not affect the detection rate, but injection over 24 h before surgery increased the detection rate on meta-regression. Concordance was 99.0 per cent and reverse concordance 97.1 per cent (rate difference 0.003, 95 per cent c.i. -0.009 to 0.015; P = 0.656, high-certainty evidence). Use of SPIO led to retrieval of slightly more SLNs (pooled mean 1.96 versus 1.89) with a higher nodal detection rate (94.1 versus 83.5 per cent; RR 1.098, 1.058 to 1.140; P < 0.001; low-certainty evidence). In meta-regression, injection over 24 h before surgery increased the SPIO nodal yield over that of RI ± BD. The skin-staining rate was 30.8 per cent (very low-certainty evidence), and possibly prevented with use of smaller doses and peritumoral injection. The performance of SPIO is comparable to that of RI ± BD. Preoperative injection increases the detection rate and nodal yield, without affecting concordance. Whether skin staining and MRI artefacts are reduced by lower dose and peritumoral injection needs to be investigated.

A holistic NMR framework to understand environmental impact: Examining the impacts of superparamagnetic iron oxide nanoparticles (SPIONs) in Daphnia magna via imaging, spectroscopy, and metabolomics.

Superparamagnetic iron oxide nanoparticles (SPIONs) are a contaminant of emerging interest, often used in the medical field as an imaging contrast agent, with additional uses in wastewater treatment and as food additives. Although the use of SPIONs is increasing, little research has been conducted on the toxic impacts to living organisms beyond traditional lethal concentration endpoints. Daphnia magna are model organisms for aquatic toxicity testing with a well understood metabolome and high sensitivity to SPIONs. Thus, as environmental concentrations continue to increase, it is becoming critical to understand their sub-lethal toxicity. Due to the paramagnetic nature of SPIONs, a range of potential nuclear magnetic resonance spectroscopy (NMR) experiments are possible, offering the potential to probe the physical location (via imaging), binding (via relaxation weighted spectroscopy), and the biochemical pathways impacted (via in vivo metabolomics). Results indicate binding to carbohydrates, likely chitin in the exoskeleton, along with a decrease in energy metabolites and specific biomarkers of oxidative stress. The holistic NMR framework used here helps provide a more comprehensive understanding of SPIONs impacts on D. magna and showcases NMR's versatility in providing physical, chemical, and biochemical insights.

Interaction of doxorubicin delivered by superparamagnetic iron oxide nanoparticles with DNA

We studied the interaction of superparamagnetic iron oxide nanoparticles (SPIONs), covered by trisodium citrate, with doxorubicin (DOX) and DNA using the spectrophotometric method. We calculated the binding parameters in the binary (DOX-SPION and SPION-DNA) and the ternary (DOX-SPION-DNA) systems. Our studies showed that the nanoparticles do not interact with DNA. We also observed that one nanoparticle loads rather a large number of DOX molecules with a quite high binding constant value (kDOX-SPION = 1.2 × 104 M−1). The DNA addition to the DOX-SPION system induces DOX release from the SPION surface and the formation of DOX-DNA complexes. The presence of nanoparticles has almost no effect on the constant of doxorubicin binding to DNA (kDOX-DNA ≈ 3 × 104 M−1). At high DNA concentrations, almost all DOX molecules bind to DNA. Accordingly, the use of SPIONs as DOX carriers does not require an increased drug dose to achieve a therapeutic effect. Thus, SPIONs are perspective nanocarriers for DOX delivery.

Enhanced Detection of Desmoplasia by Targeted Delivery of Iron Oxide Nanoparticles to the Tumour-Specific Extracellular Matrix.

Diagnostic imaging of aggressive cancer with a high stroma content may benefit from the use of imaging contrast agents targeted with peptides that have high binding affinity to the extracellular matrix (ECM). In this study, we report the use of superparamagnetic iron-oxide nanoparticles (IO-NP) conjugated to a nonapeptide, CSGRRSSKC (CSG), which specifically binds to the laminin-nidogen-1 complex in tumours. We show that CSG-IO-NP accumulate in tumours, predominantly in the tumour ECM, following intravenous injection into a murine model of pancreatic neuroendocrine tumour (PNET). In contrast, a control untargeted IO-NP consistently show poor tumour uptake, and IO-NP conjugated to a pentapeptide, CREKA that bind fibrin clots in blood vessels show restricted uptake in the angiogenic vessels of the tumours. CSG-IO-NP show three-fold higher intratumoral accumulation compared to CREKA-IO-NP. Magnetic resonance imaging (MRI) T2-weighted scans and T2 relaxation times indicate significant uptake of CSG-IO-NP irrespective of tumour size, whereas the uptake of CREKA-IO-NP is only consistent in small tumours of less than 3 mm in diameter. Larger tumours with significantly reduced tumour blood vessels show a lack of CREKA-IO-NP uptake. Our data suggest CSG-IO-NP are particularly useful for detecting stroma in early and advanced solid tumours.

SPIO nanoparticles and magnetic erythrocytes as contrast agents for biomedical and diagnostic applications

Superparamagnetic iron oxide nanoparticles (SPION) are available since many years and some of them are already approved for human use. New applications are currently emerging and the field is moving from the use of SPION as simply contrast agents, to more complex structures optimized in terms of core, size, shape and coating for different imaging modalities (e.g. MRI vs MPI), and different theranostic applications. Prof. Krishnan M. Kannan has greatly contributed to our understanding of the role of each of these parameters in shaping SPIO best function. Some of these developments are discussed in this short review just as examples. More recently, new cell-based SPIO constructs have also been optimized, moving the field from engineering the nanoparticles to the generation of hybrids cell-nanoparticle constructs. These developments have requested additional SPIO optimizations to maintain nanoparticles biocompatibility and properties and, at the same time, prevent cell damage and maintain cell functionality. Related examples from our lab are also discussed.

Cellular SPION Uptake and Toxicity in Various Head and Neck Cancer Cell Lines.

Superparamagnetic iron oxide nanoparticles (SPIONs) feature distinct magnetic properties that make them useful and effective tools for various diagnostic, therapeutic and theranostic applications. In particular, their use in magnetic drug targeting (MDT) promises to be an effective approach for the treatment of various diseases such as cancer. At the cellular level, SPION uptake, along with SPION-mediated toxicity, represents the most important prerequisite for successful application. Thus, the present study determines SPION uptake, toxicity and biocompatibility in human head and neck tumor cell lines of the tongue, pharynx and salivary gland. Using magnetic susceptibility measurements, microscopy, atomic emission spectroscopy, flow cytometry, and plasma coagulation, we analyzed the magnetic properties, cellular uptake and biocompatibility of two different SPION types in the presence and absence of external magnetic fields. Incubation of cells with lauric acid and human serum albumin-coated nanoparticles (SPIONLA-HSA) resulted in substantial particle uptake with low cytotoxicity. In contrast, uptake of lauric acid-coated nanoparticles (SPIONLA) was substantially increased but accompanied by higher toxicity. The presence of an external magnetic field significantly increased cellular uptake of both particles, although cytotoxicity was not significantly increased in any of the cell lines. SPIONs coated with lauric acid and/or human serum albumin show different patterns of uptake and toxicity in response to an external magnetic field. Consequently, the results indicate the potential use of SPIONs as vehicles for MDT in head and neck cancer.

Use of Super Paramagnetic Iron Oxide Nanoparticles as Drug Carriers in Brain and Ear: State of the Art and Challenges.

Drug delivery and distribution in the central nervous system (CNS) and the inner ear represent a challenge for the medical and scientific world, especially because of the blood–brain and the blood–perilymph barriers. Solutions are being studied to circumvent or to facilitate drug diffusion across these structures. Using superparamagnetic iron oxide nanoparticles (SPIONs), which can be coated to change their properties and ensure biocompatibility, represents a promising tool as a drug carrier. They can act as nanocarriers and can be driven with precision by magnetic forces. The aim of this study was to systematically review the use of SPIONs in the CNS and the inner ear. A systematic PubMed search between 1999 and 2019 yielded 97 studies. In this review, we describe the applications of the SPIONS, their design, their administration, their pharmacokinetic, their toxicity and the methods used for targeted delivery of drugs into the ear and the CNS.

Application of Magnetic Nano-MR Molecular Imaging Technology in the Relationship Between Meniscus Injury and Knee Joint Movement

Knee osteoarthritis (KOA) can lead to joint malformations and dysfunction. The meniscus, as the fibrous cartilage of the medial and lateral articular surfaces of the tibia, functions in load transfer, shock absorption, and knee joint stabilization. Injury of the meniscus reduces its protective effect on the knee joint and increases the risk of KOA. Early detection of meniscus injury and accurate assessment of its severity could help to clinically formulate corresponding treatment plans, delay disease progression, and reduce the risk of KOA. Magnetic resonance imaging (MRI) can clearly characterize the tissue structure of the meniscus in all directions, which is convenient for observing the damage to it. However, the sensitivity of traditional MRI to cartilage tissue is still limited. Superparamagnetic iron oxide nanoparticles (SPION), as a nano-biomaterial with superparamagnetic properties, can enhance MR signal intensity and imaging sensitivity. The use of SPION as a contrast agent for MRI diagnosis of meniscus injury may help to improve the diagnostic accuracy. In this study, the results of arthroscopy were used as a gold standard to compare the diagnostic value of traditional MRI and MRI+SPION in meniscus injury. We found that SPION could significantly improve the sensitivity, specificity, and accuracy of MRI in diagnosing meniscus injury. According to the classification of the severity of meniscus injury by MRI+SPION, six degrees of freedom of knee joints were compared in each group, and major differences were found in each degree of freedom of knee joints in the patients with different severity grades. The more severe the injury, the smaller the range of degrees of freedom of the knee. The above results show that the knee joint activity of patients with meniscus injury can be evaluated according to magnetic nano-magnetic resonance molecular imaging technology, and the corresponding clinical treatment plan can be made according to the diagnosis and evaluation results.

Use of SPIONs for Removal of Heavy Metal and its Isotherm Studies

The presence of heavy metals is unpreventable in the current era leading to anthropogenic pollution and production of toxicants such as hexavalent chromium [Cr(VI)] to the environment. It is a common, known carcinogen to humans through inhalation as well as ingestion. With proper treatment of the effluents from industrial activity, the concentration of Cr(VI) would be minified and eliminated. Superparamagnetic iron oxide nanoparticles (SPIONs) were once employed to evaluate its absorption efficiency against Cr(VI). The research now centered the concern on Cr(VI) elimination with SPIONS with carbon and used in batch adsorption study with optimized pH, adsorbent, and adsorbent-adsorbate concentrations. The adsorption then evaluated the result by Langmuir, Freundlich, and Temkin isotherms.

Superparamagnetic iron oxide nanoparticles (SPIONs) as a multifunctional tool in various cancer therapies.

Over the past two decades nanotechnology has become an important part of novel medical research. Researchers have made great progress in developing nanotechnology applications used for detecting and treating oncological diseases. Recently, many research groups have focused on the use of superparamagnetic iron oxide nanoparticles (SPIONs) in cancer treatment. Due to the range of therapeutic properties and possibilities of various modifications, SPIONs are a promising and multifunctional tool in various cancer therapies and may help to overcome the limitations of conventional therapies. Moreover, it is still necessary to develop new methods of treatment with expected properties, such as lower toxicity, long-lasting effectiveness and higher selectivity. Analyzing the literature data, we found that currently SPIONs are used in the transport of drugs, immunotherapy and hyperthermia. The main aim of this review is to present various cancer treatment therapies utilizing SPIONs, the importance of the experiments carried out by research groups and further perspectives in the nanotechnological use of SPIONs.

Colloidal stability of superparamagnetic iron oxide nanoparticles in the central nervous system: a review.

Superparamagnetic iron oxide nanoparticles (SPIONs) consist of nanosized metallic-based particles with unique magnetic properties. Their potential in both diagnostic and therapeutic applications in the CNS is at the source of an expanding body of the literature in recent years. Colloidal stability of nanoparticles represents their ability to resist aggregation and is a central aspect for the use of SPION in biological environment such as the CNS. This review gives a comprehensive update of the recent developments and knowledge on the determinants of colloidal stability of SPIONs in the CNS. Factors leading to aggregate formation and the repercussions of colloidal instability of SPION are reviewed in detail pertaining to their use in the CNS.

Functionalized Magnetic PLGA Nanospheres for Targeting and Bioimaging of Breast Cancer.

Superparamagnetic iron oxide nanoparticles (SPIONs) are actively used as highly sensitive imaging probes to provide contrast in MRI. In this study, we propose the use of SPIONs encapsulated with antibody-conjugated poly(lactic-co-glycolic acid) (PLGA) as a potent theragnostic agent. The SPIONs were synthesized by a chemical co-precipitation method of ferric and ferrous ions, and subsequently encapsulated with PLGA by using an emulsification-diffusion method. Herceptin was chemically conjugated to the SPION-encapsulating PLGA nanoparticles to target the human epidermal growth factor receptor 2 (Her2/neu) overexpressing breast cancers. FACS and MR molecular imaging revealed that the Her2/neu overexpressing cell line showed a stronger contrast enhancement than the Her2/neu non-expressing cell lines, and the signal intensity of in vivo MR imaging decreased as the concentration of Herceptin increased. This strategy of encapsulating SPIONs with PLGA will be highly useful in functionalizing magnetic nanoparticles and improving the diagnostic and therapeutic efficacy of a wide array of cancer treatments.

An Innovative Application of Super-Paramagnetic Iron Oxide Nanoparticles for Magnetic Separation

In the last decades, iron oxide nanoparticle application has taken root in several technological fields, such as magnetic separation of biomolecules, biosensors, bio-fuel production, nano-devices and nano-adsorption. Various approaches can be found for the magnetic nanoparticle manufacturing. Among them a new technology to manufacture core-cell super-paramagnetic iron oxide nanoparticles (SPIONs), based on a vapour composition using single ion precursors, like cyclodextrines, has been recently developed. In this paper, we present the synthesis of functionalized SPIONs as well as the modelling for an innovative application of this magnetic nanotechnology. It consists on the use of SPIONs to trap target organic or inorganic molecules in a continuous-flow apparatus. SPIONs with proper ligands are immobilized on a magnetic surface. On that surface, the solution containing target molecules is circulated. We modelled the magnetic properties of the magnetic surface and SPIONs as well as the velocity of liquid needed in order to avoid removal of nanoparticles by the solution flow.

A novel approach to analyze lysosomal dysfunctions through subcellular proteomics and lipidomics: the case of NPC1 deficiency

Superparamagnetic iron oxide nanoparticles (SPIONs) have mainly been used as cellular carriers for genes and therapeutic products, while their use in subcellular organelle isolation remains underexploited. We engineered SPIONs targeting distinct subcellular compartments. Dimercaptosuccinic acid-coated SPIONs are internalized and accumulate in late endosomes/lysosomes, while aminolipid-SPIONs reside at the plasma membrane. These features allowed us to establish standardized magnetic isolation procedures for these membrane compartments with a yield and purity permitting proteomic and lipidomic profiling. We validated our approach by comparing the biomolecular compositions of lysosomes and plasma membranes isolated from wild-type and Niemann-Pick disease type C1 (NPC1) deficient cells. While the accumulation of cholesterol and glycosphingolipids is seen as a primary hallmark of NPC1 deficiency, our lipidomics analysis revealed the buildup of several species of glycerophospholipids and other storage lipids in selectively late endosomes/lysosomes of NPC1-KO cells. While the plasma membrane proteome remained largely invariable, we observed pronounced alterations in several proteins linked to autophagy and lysosomal catabolism reflecting vesicular transport obstruction and defective lysosomal turnover resulting from NPC1 deficiency. Thus the use of SPIONs provides a major advancement in fingerprinting subcellular compartments, with an increased potential to identify disease-related alterations in their biomolecular compositions.

Hydrophilic packaging of iron oxide nanoclusters for highly sensitive imaging

Superparamagnetic iron oxide nanoparticles (SPIONs) are used as imaging probes to provide contrast in magnetic resonance images. Successful use of SPIONs in targeted applications greatly depends on their ability to generate contrast, even at low levels of accumulation, in the tissue of interest. In the present study, we report that SPION nanoclusters packaged to a controlled size by a hyperbranched polyglycerol (HPG) can target tissue defects and have a high relaxivity of 719 mM−1 s−1, which was close to their theoretical maximal limit. The resulting nanoclusters were able to identify regions of defective vasculature in an ischemic murine hindlimb using MRI with iron doses that were 5–10 fold lower than those typically used in preclinical studies. Such high relaxivity was attributed to the molecular architecture of HPG, which mimics that of the water retentive polysaccharide, glycogen. The results of this study will be broadly useful in sensitive imaging applications.

Superparamagnetic iron oxide nanoparticles as a multimodal contrast agent for up to five imaging modalities

labeled nanometer sized colloids are injected sub-dermally or peri-tumourally, and then imaged using a gamma camera/SPECT (before surgery) and a gamma probe (during surgery). A blue dye injected prior to surgery may serve to visualize the SLN intra-operatively. When the SLN is found, it is removed by invasive surgery and cancer infiltration is examined using histology. The lack of precise anatomic information in the scintigraphic images and the non-specificity of the tracer, however, often limit the preoperative planning and the identification of the SLN. Multimodal approaches in the clinic, such as the next generation hybrid systems based on combined MR/PETsystems, are expected to address several of these issues. In the pre-clinical setting, an even faster growing segment for medical imaging‐multimodal systems including optical methods is concurrently emerging. Interestingly, there exist still no commercially available clinical contrast agent that can be used for even two modalities, and research has shown functionality for only a couple imaging modalities at a time. Our aim is to develop novel multimodality contrast agents and methodology for such systems to meet new needs for quantitative and high-resolution imaging. In this perspective, superparamagnetic iron oxide nanoparticles (SPIO-NPs) are emerging as a highly attractive approach. SPIO-NPs can be observed by MRI as signal voids in the MR image and SPIO-NPs have been approved as MRI contrast agents for more than a decade with applications including lymph node detection. We propose the use of SPIO-NPs as a multimodal contrast agent by attaching radionuclides and fluorophores to the surface of the nanoparticles, for, respectively, SPECT, PET, and optical imaging methods. Moreover, the particles also inherently functions as contrast media for a new imaging technique called magnetomotive ultrasound imaging. Thus, the very same particles can be used as a contrast agent for up to five modalities, depending on the type of surface modification. We expect the following improvements for the work-flow of cancer patients undergoing lymph node surgery: • One single injection of tracer, and thereby no timing issues experienced with the dye used today. This means less preparation time prior to surgery, and reduced risk of lymph edema due to excessive removal of colored lymph nodes. • Improved staging due to truly combined information in a PET/MR system including tracer migration analysis.

Transient modulation of acetylcholinesterase activity caused by exposure to dextran-coated iron oxide nanoparticles in brain of adult zebrafish

Superparamagnetic iron oxide nanoparticles (SPIONs) are of great interest in nanomedicine due to their capability to act simultaneously as a contrast agent and as a targeted drug delivery system. At present, one of the biggest concerns about the use of SPIONs remains around its toxicity and, for this reason, it is important to establish the safe upper limit for each use. In the present study, SPION coated with cross-linked aminated dextran (CLIO-NH2) were synthesized and their toxicity to zebrafish brain was investigated. We have evaluated the effect of different CLIO-NH2 doses (20, 50, 100, 140 and 200mg/kg) as a function of time after exposure (one, 16, 24 and 48h) on AChE activity and ache expression in zebrafish brain. The animals exposed to 200mg/kg and tested 24h after administration of the nanoparticles have shown decreased AChE activity, reduction in the exploratory performance, significantly higher level of ferric iron in the brains and induction of casp8, casp 9 and jun genes. Taken together, these findings suggest acute brain toxicity by the inhibition of acetylcholinesterase and induction of apoptosis.

Stem cell tracking using iron oxide nanoparticles.

Superparamagnetic iron oxide nanoparticles (SPIONs) are an exciting advancement in the field of nanotechnology. They expand the possibilities of noninvasive analysis and have many useful properties, making them potential candidates for numerous novel applications. Notably, they have been shown that they can be tracked by magnetic resonance imaging (MRI) and are capable of conjugation with various cell types, including stem cells. In-depth research has been undertaken to establish these benefits, so that a deeper level of understanding of stem cell migratory pathways and differentiation, tumor migration, and improved drug delivery can be achieved. Stem cells have the ability to treat and cure many debilitating diseases with limited side effects, but a main problem that arises is in the noninvasive tracking and analysis of these stem cells. Recently, researchers have acknowledged the use of SPIONs for this purpose and have set out to establish suitable protocols for coating and attachment, so as to bring MRI tracking of SPION-labeled stem cells into common practice. This review paper explains the manner in which SPIONs are produced, conjugated, and tracked using MRI, as well as a discussion on their limitations. A concise summary of recently researched magnetic particle coatings is provided, and the effects of SPIONs on stem cells are evaluated, while animal and human studies investigating the role of SPIONs in stem cell tracking will be explored.

Multifunctional stable fluorescent magnetic nanoparticles

Because of their multifunctionality and unique magnetic properties, superparamagnetic iron oxide nanoparticles (SPIONs) have been recognized as very promising materials for various biomedical applications. The main difficulty with the use of SPIONs as multimodal bioimaging agents is their lack of fluorescence. Since cells can act as extremely efficient filters for the elution of surface-bound fluorescent tags with nanoparticles, the surface loaded fluorescence dyes significantly decay after a short period of time. Here, for the first time, we introduce novel, engineered multimodal SPIONs with a permanent fluorescence capability, the study of which can lead to a deeper understanding of biological processes at the biomolecular level, greatly influencing molecular diagnostics, imaging and therapeutic applications.

The internalization pathway, metabolic fate and biological effect of superparamagnetic iron oxide nanoparticles in the macrophage-like RAW264.7 cell

The potential applications of superparamagnetic iron oxide nanoparticles (SPIONs) in several nanomedical fields have attracted intense interest based on the cell-nano interaction. However, the mechanisms underlying cell uptake, the intracellular trail, final fate and the biological effects of SPIONs have not yet been clearly elucidated. Here, we showed that multiple endocytic pathways were involved in the internalization process of SPIONs in the RAW264.7 macrophage. The internalized SPIONs were biocompatible and used three different metabolic pathways: The SPIONs were distributed to daughter cells during mitosis; they were degraded in the lysosome and free iron was released into the intracellular iron metabolic pool; and, the intact SPIONs were potentially exocytosed out of the cells. The internalized SPIONs did not induce cell damage but affected iron metabolism, inducing the upregulation of ferritin light chain at both the mRNA and protein levels and ferroportin 1 at the mRNA level. These results may contribute to the development of nanobiology and to the safe use of SPIONs in medicine when administered as a contrast medium or a drug delivery tool.