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Un-complexed polynuclear ferric oxyhydroxide cannot be administered safely or effectively to patients. When polynuclear iron cores are formed with carbohydrates of various structures, stable complexes with surface carbohydrates driven by multiple interacting sites and forces are formed. These complexes deliver iron in a usable form to the body while avoiding the serious adverse effects of un-complexed forms of iron, such as polynuclear ferric oxyhydroxide. The rate and extent of plasma clearance and tissue biodistribution is variable among the commercially available iron-carbohydrate complexes and is driven principally by the surface characteristics of the complexes which dictate macrophage opsonization. The surface chemistry differences between the iron-carbohydrate complexes results in significant differences in in vivo pharmacokinetic and pharmacodynamic profiles as well as adverse event profiles, demonstrating that the entire iron-carbohydrate complex furnishes the pharmacologic action for these complex products. Currently available physicochemical characterization methods have limitations in biorelevant matrices resulting in challenges in defining critical quality attributes for surface characteristics for this class of complex nanomedicines.

Magnetic nanoparticles are widely studied for their use in various therapeutic and diagnostic purposes. As biomaterials, their biocompatibility is as important as their magnetic properties. Iron nitride (Fe x N y ) has excellent magnetic properties, and thus Fe x N y nanoparticles could be useful as potential biomaterials. However, the biocompatibility of Fe x N y nanoparticles is yet to be investigated. In this study, we assessed the biocompatibility of Fe x N y nanoparticles by evaluating their direct-contact cytotoxicity compared with that of magnetite nanoparticles (MNPs). Rat fibroblasts were incubated with the nanoparticle samples dispersed in culture medium at concentrations of 10, 50, and 100 μg/ml. The DNA concentration measurement, MTT assay, and trypan blue exclusion test were conducted after days 1 and 3 of incubation. After day 1, the cell viability decreased, and cell death increased with increasing sample concentration when compared with the control. However, after day 3, there were no significant differences when compared with the control, irrespective of the sample concentrations. Further, there were no significant differences between the Fe x N y nanoparticles and MNPs at the same concentrations in all the cytotoxicity evaluation tests. Therefore, it is suggested that Fe x N y nanoparticles might be as cytocompatible as the conventional MNPs., (© 2021 Wiley Periodicals LLC.)

Microbial exopolysaccharides (EPSs) have recently served as an efficient substrate for the production of biocompatible metal nanoparticles (NPs) given their favorable stabilizing and reducing properties due to the presence of polyanionic functional groups in their structure. In the present work, Pantoea sp. BCCS 001 GH was used to produce EPS-stabilized biogenic Fe NPs as a complex through a novel biosynthesis reaction. Physicochemical characterization of the EPS-Fe complex was performed, indicating high thermal stability, desirable magnetic properties due to the uniform distribution of the Fe NPs with the average size of ∼10 nm and spherical shape within the EPS matrix. In addition, the in vivo toxicity of the EPS-stabilized Fe NPs was evaluated to investigate their potential for the treatment of iron deficiency anemia. Biological blood parameters and organ histology studies confirmed very high safety of the biosynthesized composite, making EPS-Fe a suitable candidate with an economical and environment friendly synthesis method for a wide spectrum of potential fields in medicine.

We previously identified a novel nanomagnetic particle, N,N'-bis(salicylidene)ethylenediamine iron [Fe(Salen)]. Fe(Salen) not only shows antitumor effects but also magnetic properties. We found that Fe(Salen) can be used for magnet-guided drug delivery and visualization of accumulated drug by magnetic resonance imaging (MRI) because of its magnetism. In addition, Fe(Salen) can generate heat by itself when exposed to an alternating current magnetic field (AMF), resulting in a hyperthermia effect. Herein, we partly elucidated the antitumor mechanism of Fe(Salen) and carried out an i.v. repeated dose toxicity study to decide the therapeutic amount. Furthermore, we evaluated the antitumor effect of selective intra-arterial injection or i.v. injection of Fe(Salen) by catheter and the hyperthermia effect of Fe(Salen) when exposed to AMF in vivo. We used a rabbit model grafted with VX2 cells (rabbit squamous cell carcinoma) on the right leg. Intra-arterial injection of Fe(Salen) showed a greater antitumor effect than did i.v. injection. The combination of Fe(Salen) intra-arterial injection and AMF exposure showed a greater antitumor effect than did either Fe(Salen) or methotrexate (MTX) without AMF exposure, suggesting that AMF exposure greatly enhanced the antitumor effect of Fe(Salen) by arterial injection by catheter. This is the first report that the effectiveness of Fe(Salen) was evaluated in the point of administration route; that is, selective intra-arterial injection by catheter. Taken together, these results indicate a new administration route; that is, selective arterial injection of Fe(Salen) by catheter, and the development of a new strategy of simultaneous hyperthermia-chemotherapy in the future., (© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Therapeutic nanosystems which can be triggered by the distinctive tumor microenvironment possess great selectivity and safety to treat cancers via in situ transformation of nontoxic prodrugs into toxic therapeutic agents. Here, we constructed intelligent, magnetic targeting, and tumor microenvironment-responsive nanocatalysts that can acquire oxidation therapy of cancer via specific reaction at tumor site. The magnetic nanoparticle core of iron carbide-glucose oxidase (Fe 5 C 2 -GOD) achieved by physical absorption has a high enzyme payload, and the manganese dioxide (MnO 2 ) nanoshell as an intelligent "gatekeeper" shields GOD from premature leaking until reaching tumor tissue. Fe 5 C 2 -GOD@MnO 2 nanocatalysts maintained inactive in normal cells upon systemic administration. On the contrary, after endocytosis by tumor cells, tumor acidic microenvironment induced decomposition of MnO 2 nanoshell into Mn 2+ and O 2 , meanwhile releasing GOD. Mn 2+ could serve as a magnetic resonance imaging (MRI) contrast agent for real-time monitoring treatment process. Then the generated O 2 and released GOD in nanocatalysts could effectively exhaust glucose in tumor cells, simultaneously generating plenty of H 2 O 2 which may accelerate the subsequent Fenton reaction catalyzed by the Fe 5 C 2 magnetic core in mildly acidic tumor microenvironments. Finally, we demonstrated the tumor site-specific production of highly toxic hydroxyl radicals for enhanced anticancer therapeutic efficacy while minimizing systemic toxicity in mice.

As a promising cell tracking technology, 19F MRI suffers from low sensitivity. Here, fluorinated nanoemulsions with a unified 19F signal and paramagnetic relaxation enhancement were developed as 19F MRI cellular tracers with high stability, size controllability, biocompatibility, cellular uptake, and dual-modality for sensitive in vivo RAW264.7 cell tracking.

Metal nanoparticles have been reported to influence plant growth and productivity. However, the molecular mechanisms underlying the effects have not been completely understood yet. Current work describes the physio-biochemical basis of iron sulfide nanoparticle induced growth and yield enhancement in Brassica juncea. Iron sulfide nanoparticles (0, 2, 4, 6, 8 and 10 ppm) were used for foliar treatment of B. juncea at 30, 45 and 60 days after sowing, under field conditions. Foliar treatment of 4 ppm iron sulfide nanoparticle solution at 30 days after sowing brought maximal enhancement in agronomic attributes of the treated plants. Results of assays i.e. total chlorophyll, electrolyte leakage, Malondialdehyde (MDA), proline, H 2 O 2 and antioxidant enzyme activities indicated the benign effect of iron sulfide nanoparticles on plants. Consequently, improved redox status of the treated plants, enabled them to assimilate higher photosynthate. The augmentation in growth and seed yield in iron sulfide nanoparticle treated plants was amply supported by activation of RUBISCO small subunit (rubisco S), RUBISCO large subunit (rubisco L), glutamine synthetase (gs) and glutamate synthase (gogat) genes. Thus, iron sulfide nanoparticle induced growth and yield enhancement is proposed to be mediated through activation of carbon and nitrogen assimilatory pathways at specific growth stage. The iron content in the leaves and root tissues of the treated plants was also significantly improved., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Recently, magnetic photothermal nanomaterials have emerged as a new class of bio-nanomaterials for application in cancer diagnosis and therapy. Hence, we developed a new kind of magnetic nanomaterials, iron diselenide (FeSe(2)) nanoparticles, for multimodal imaging-guided photothermal therapy (PTT) to improve the efficacy of cancer treatment. By controlling the reaction time and temperature, FeSe(2) nanoparticles were synthesized by a simple solution-phase method. After modification with polyethylene glycol (PEG), the obtained FeSe(2)-PEG nanoparticles showed high stability under various physiological conditions. FeSe(2)-PEG could serve as a T2-weighted magnetic resonance (MR) imaging contrast agent because of its strong superparamagnetic properties, with its r(2) relaxivity determined to be 133.38 mM(-1) S(-1), a value higher than that of the clinically used Feridex. On the other hand, with high absorbance in the near-infrared (NIR) region, FeSe(2)-PEG also appeared to be a useful contrast agent for photoacoustic imaging (PA) as well as an effective photothermal agent for PTT cancer treatment, as demonstrated in our animal tumor model experiments. Moreover, long-term toxicity tests have proven that FeSe(2)-PEG nanoparticles after systematic administration rendered no appreciable toxicity to the treated animals, and could be gradually excreted from the major organs of mice. Our work indicates that FeSe(2)-PEG nanoparticles would be a new class of theranostic agents promising for application in bioimaging and cancer therapy.

Aim: Magnetic field guided drug targeting holds promise for more effective cancer treatment. Intravascular application of magnetic nanoparticles, however, bears the risk of potentially important, yet poorly understood side effects, such as off-target accumulation in endothelial cells., Materials & Methods: Here, we investigated the influence of shear stress (0-3.22 dyn/cm(2)), exposure time (5-30 min) and endothelial activation on the uptake of ferromagnetic carbon-encapsulated iron carbide nanomagnets into endothelial cells in an in vitro flow cell model., Results: We found that even moderate shear stresses typically encountered in the venous system strongly reduce particle uptake compared with static conditions. Interestingly, a pronounced particle uptake was observed in inflamed endothelial cells., Conclusion: This study highlights the importance of relevant exposure scenarios accounting for physiological conditions when studying particle-cell interactions as, for example, shear stress and endothelial activation are major determinants of particle uptake. Such considerations are of particular importance with regard to successful translation of in vitro findings into (pre-)clinical end points.

Synthetic zero-valent nano-iron (nZVI) compounds are finding numerous applications in environmental remediation owing to their high chemical reactivity and versatile catalytic properties. Studies were carried out to assess the effects of three types of industrially relevant engineered nZVI on phytoplankton growth, cellular micromorphology and metabolic status. Three marine microalgae (Pavlova lutheri, Isochrysis galbana and Tetraselmis suecica) were grown on culture medium fortified with the nano-Fe compounds for 23 days and subsequent alterations in their growth rate, size distribution, lipid profiles and cellular ultrastructure were assessed. The added nano Fe concentrations were either equimolar with the EDTA-Fe conventionally added to the generic f/2 medium (i.e. 1.17 × 10(-5)M), or factor 10 lower and higher, respectively. We provide evidence for the: (1) broad size distribution of nZVI particles when added to the nutrient rich f/2 media with the higher relative percentage of the smallest particles with the coated forms; (2) normal algal growth in the presence of all three types of nZVIs with standard growth rates, cellular morphology and lipid content comparable or improved when compared to algae grown on f/2 with EDTA-Fe; (3) sustained algal growth and normal physiology at nZVI levels 10 fold below that in f/2, indicating preference to nanoparticles over EDTA-Fe; (4) increased total cellular lipid content in T. suecica grown on media enriched with uncoated nZVI25, and in P. lutheri with inorganically coated nZVI(powder), when compared at equimolar exposures; (5) significant change in fatty acid composition complementing the nZVI(powder)-mediated increase in lipid content of P. lutheri; (6) a putative NP uptake mechanism is proposed for I. galbana via secretion of an extracellular matrix that binds nZVIs which then become bioavailable via phagocytotic membrane processes., (Copyright © 2012 Elsevier B.V. All rights reserved.)