Iron Oxide Core Research Articles

Evaluation of the Physicochemical Properties of the Iron Nanoparticle Drug Products: Brand and Generic Sodium Ferric Gluconate.

Complex iron nanoparticle-based drugs are one of the oldest and most frequently administered classes of nanomedicines. In the US, there are seven FDA-approved iron nanoparticle reference drug products, of which one also has an approved generic drug product (i.e., sodium ferric gluconate (SFG)). These products are indicated for the treatment of iron deficiency anemia and are administered intravenously. On the molecular level, iron nanomedicines are colloids composed of an iron oxide core with a carbohydrate coating. This formulation makes nanomedicines more complex than conventional small molecule drugs. As such, these products are often referred to as nonbiological complex drugs (e.g., by the nonbiological complex drugs (NBCD) working group) or complex drug products (e.g., by the FDA). Herein, we report a comprehensive study of the physiochemical properties of the iron nanoparticle product SFG. SFG is the single drug for which both an innovator (Ferrlecit) and generic product are available in the US, allowing for comparative studies to be performed. Measurements focused on the iron core of SFG included optical spectroscopy, inductively coupled plasma mass spectrometry (ICP-MS), X-ray powder diffraction (XRPD), 57Fe Mössbauer spectroscopy, and X-ray absorbance spectroscopy (XAS). The analysis revealed similar ferric-iron-oxide structures. Measurements focused on the carbohydrate shell comprised of the gluconate ligands included forced acid degradation, dynamic light scattering (DLS), analytical ultracentrifugation (AUC), and gel permeation chromatography (GPC). Such analysis revealed differences in composition for the innovator versus the generic SFG. These studies have the potential to contribute to future quality assessment of iron complex products and will inform on a pharmacokinetic study of two therapeutically equivalent iron gluconate products.

Iron Oxide Nanoparticle Coatings Dictate Cell Outcomes Despite the Influence of Protein Coronas.

A critical issue in nanomedicine is to understand the complex dynamics that dictate the interactions of nanoparticles (NPs) with their biological milieu. The most exposed part of a nanoparticle is its surface coating, which comes into contact with the biological medium and adsorbs proteins, forming what is known as a protein corona (PC). It is assumed that this PC mainly dictates the nanoparticle-cell interactions. As such, we set out to analyze how different coatings on iron oxide nanoparticles (MNPs) affect the composition of the PC that forms on top of them, and how these newly formed coronas influence the uptake of MNPs by macrophages and tumor cells, their subcellular location upon internalization, and their intracellular degradation. We found that different superficial charges of the coatings did not affect the PC composition, with an enrichment in proteins with affinity for divalent ions regardless of the type of coating. The iron oxide core of the MNP might become exposed to the biological medium, influencing the proteins that constitute the PCs. The presence of enzymes with hydrolase activity in the PC could explain the degradation of the coatings when they come into contact with the biological media. In terms of MNP internalization by cells, coatings mainly determine the endocytic pathways used, especially in terms of receptor-mediated endocytosis. However, the increase in hydrodynamic size provoked by the formation of the associated corona drives uptake mechanisms like macropinocytosis. Once inside the cells, the PC protected the NPs in their intracellular transit to lysosomes, where they were fully degraded. This understanding of how coatings and PCs influence different cellular processes will help design improved NPs for biomedical applications, taking into account the influence of the coating and corona on the biology of the NPs.

Synthesis of core@shell nanoparticles functionalized with folic acid-modified PCL-co-PEGMA copolymer for methotrexate delivery

Cancer is responsible for many fatalities and it is considered a public health problem. The side effects caused by conventional treatment are aggressive and painful to patients and can be reduced using nanomaterials that allows action in specific sites, making the cancer treatment more efficient, improving patient life’s quality. Many kinds of nanoparticles that can be used, among these the block copolymer functionalized iron oxide nanoparticles stand out due to their simultaneous interaction with hydrophobic and hydrophilic drugs. The evaluation of these platforms properties allows optimizing their action in the human body, enhancing its biodistribution and targeting a specific region in the organism. The encapsulation efficiency and the controlled release profile is strictly dependent on the size, morphology, and interactions of the copolymer blocks. In this work, it was studied the synthesis of a hybrid nanoplatform composed of an inorganic core (iron oxide) and a polymeric shell (PCL-co-PEGMA block copolymer modified with folic acid). FTIR and 1H NMR allowed the confirmation of the nanoplatform synthesis. Particles around 180 nm stable at physiological pH were obtained, allowing its application in different regions of the human body. The encapsulation efficiency of methotrexate was approximately 95%. The drug delivery assays indicated that the nanoplatform is less active at pH 2; the presence of reduced glutathione enhanced the methotrexate release, reaching almost 50% methotrexate release after 96 h of analysis. The release efficiency of the nanoplatform allowed to identify its potential as a controlled drug delivery system.

Smart Nanoformulation Based on Polymeric Magnetic Nanoparticles and Vincristine Drug: A Novel Therapy for Apoptotic Gene Expression in Tumors.

Background: Advanced nanobiotechnology provides safe and efficient drug delivery systems to deliver chemotherapy that targets cancer cells efficiently. Methods: A polymeric-magnetic nanocarrier was composed of a dextran (DEX) shell, a superparamagnetic iron oxide (SPION) core and was conjugated with folate (FA) to carry the anticancer drug vincristine (VNC) in Tera-1 testicular tumor cells. The molecular mechanisms by which apoptosis was induced were analyzed using flow cytometry and qPCR, which exhibited anticancer activity of nanoparticles (NPs). Results: This nanocarrier revealed a controlled release of VNC in citrate and phosphate buffer solutions that were maintained at pH 5.5 and pH 7.4, respectively. The Inhibitory concentration (IC50) values were greater than 5 mg/mL and displayed ten times higher cytotoxicity than the comparable free drug concentration. The Caspase-9 and P53 expressions were increased, whereas P21 and AKt1 decreased noticeably in the treated cells. The results point to the possible activation of apoptosis following treatment with NPs loaded with vincristine.

Insight to sorption mechanism employing nanocomposite: Case study of toxic species removal

Iron oxide-silica nanocomposite synthesized by one-pot co-precipitation method was evaluated for its applicability as sorbents for removal of toxic species like inorganic metal ions (UO22+, Zn2+, Cu2+, Ni2+, Co2+) and cationic dyes (MB and R6G) from aqueous streams at room temperature. The detailed structural analysis revealed the formation of crystalline iron oxide core with amorphous silica shell. The zeta potential measurements of surface charge helped in assessing the applicability of the sorbents. The magnetic property of the sorbent, as evaluated from magnetic measurements helped in its easy separation from solution using external magnetic field. The high porosity and large surface area of sorbent contributed to its excellent sorption efficiency. The efficiency of magnetic nano-composites was analyzed with respect to sorption kinetics (rate and kinetics order), initial concentration of toxic species (equilibrium conditions) and weight of sorbent. The optimum pH for uptake was in the range of 5–6. Extensive modelling of sorption data helped in getting an insight to the mechanism of metal ion sorption. The selectivity towards uptake of MB (MB) as opposed to that of Rhodamine 6G (R6G) was quite intriguing and detailed studies were carried out to understand this. Since the bare nanosorbent showed no selectivity in sorption of metal ions, modification was carried out to enhance selectivity with respect to uranyl ion.

Investigation of the Characteristics of New, Uniform, Extremely Small Iron-Based Nanoparticles as T1 Contrast Agents for MRI.

ObjectiveThe purpose of this study was to evaluate the magnetic resonance (MR) characteristics and applicability of new, uniform, extremely small iron-based nanoparticles (ESIONs) with 3–4-nm iron cores using contrast-enhanced magnetic resonance angiography (MRA).Materials and MethodsSeven types of ESIONs were used in phantom and animal experiments with 1.5T, 3T, and 4.7T scanners. The MR characteristics of the ESIONs were evaluated via phantom experiments. With the ESIONs selected by the phantom experiments, animal experiments were performed on eight rabbits. In the animal experiments, the in vivo kinetics and enhancement effect of the ESIONs were evaluated using half-diluted and non-diluted ESIONs. The between-group differences were assessed using a linear mixed model. A commercially available gadolinium-based contrast agent (GBCA) was used as a control.ResultsAll ESIONs showed a good T1 shortening effect and were applicable for MRA at 1.5T and 3T. The relaxivity ratio of the ESIONs increased with increasing magnetic field strength. In the animal experiments, the ESIONs showed peak signal intensity on the first-pass images and persistent vascular enhancement until 90 minutes. On the 1-week follow-up images, the ESIONs were nearly washed out from the vascular structures and organs. The peak signal intensity on the first-pass images showed no significant difference between the non-diluted ESIONs with 3-mm iron cores and GBCA (p = 1.000). On the 10-minutes post-contrast images, the non-diluted ESIONs showed a significantly higher signal intensity than did the GBCA (p < 0.001).ConclusionIn the phantom experiments, the ESIONs with 3–4-nm iron oxide cores showed a good T1 shortening effect at 1.5T and 3T. In the animal experiments, the ESIONs with 3-nm iron cores showed comparable enhancement on the first-pass images and superior enhancement effect on the delayed images compared to the commercially available GBCA at 3T.

Magnetic Iron Oxide Cores with Attached Gold Nanostructures Coated with a Layer of Silica: Easily Homogeneously Deposited New Nanomaterial for Surface-Enhanced Raman Scattering Measurements

Magnetic Iron Oxide Cores with Attached Gold Nanostructures Coated with a Layer of Silica: Easily Homogeneously Deposited New Nanomaterial for Surface-Enhanced Raman Scattering Measurements

A highly selective iron oxide-based imaging nanoparticle for long-term monitoring of drug-induced tumor cell apoptosis.

The ability to visualize and quantify apoptosis in vivo is critical to monitoring the disease response to treatment and providing prognostic information. However, the application of current apoptosis labeling probes faces significant challenges including nonspecific tissue uptake, inefficient apoptotic cell labeling and short monitoring windows. Here we report a highly specific apoptosis labeling nanoparticle (NP) probe with Pisum sativum agglutinin (PSA) as a tumor targeting ligand for prolonged in vivo apoptosis imaging. The NP (namely, IONP-Neu-PSA) consists of a magnetic iron oxide core (IONP) conjugated with PSA, and a reporter fluorophore. IONP-Neu-PSA demonstrated minimal cytotoxicity and high labeling specificity towards apoptotic cells in vitro. When applied in vivo, IONP-Neu-PSA tracks apoptotic tumors for a prolonged period of two weeks under near-IR imaging with low background noise. Moreover, IONP-Neu-PSA possesses T2 contrast enhancing properties that can potentially enable apoptosis detection by magnetic resonance imaging (MRI). The high specificity for apoptotic cells, sustained fluorescence signals, and non-invasive imaging capability exhibited by IONP-Neu-PSA make it a versatile tool for cancer treatment monitoring and pathological research.

OBP-functionalized/hybrid superparamagnetic nanoparticles for Candida albicans treatment.

Infections caused by the opportunistic yeast Candida albicans are one of the major life threats for hospitalized and immunocompromised patients, as a result of antibiotic and long-term antifungal treatment abuse. Odorant binding proteins can be considered interesting candidates to develop systems able to reduce the proliferation and virulence of this yeast, because of their intrinsic antimicrobial properties and complexation capabilities toward farnesol, the major quorum sensing molecule of Candida albicans. In the present study, a hybrid system characterized by a superparamagnetic iron oxide core functionalized with bovine odorant binding protein (bOBP) was successfully developed. The nanoparticles were designed to be suitable for magnetic protein delivery to inflamed areas of the body. The inorganic superparamagnetic core was characterized by an average diameter of 6.5 ± 1.1 nm and a spherical shape. Nanoparticles were functionalized by using 11-phosphonoundecanoic acid as spacer and linked to bOBP via amide bonds, resulting in a concentration level of 26.0 ± 1.2 mg bOBP/g SPIONs. Finally, both the biocompatibility of the developed hybrid system and the fungistatic activity against Candida albicans by submicromolar OBP levels were demonstrated by in vitro experiments.

Zero-valent iron core–iron oxide shell nanoparticles coated with silica and gold with high saturation magnetization

A new type of gold-coated magnetic nanoparticle with strongly magnetic zero-valent iron core–iron oxide shell were synthesized.

A versatile strategy to synthesize sugar ligand coated superparamagnetic iron oxide nanoparticles and investigation of their antibacterial activity

For the time being, a great attention has been given to the search of green and reusable materials with antibacterial properties. The present research focused on the design and synthesis of hybrid structures constituting superparamagnetic iron oxide nanoparticles (SPIONs) coated with sugar ligands (SL), synthesized using a green and efficient microwave (MW)-assisted hydrothermal synthesis. The sugar ligands were selectively engineered to obtain antibacterial characteristics towards multi-drug resistant bacterial strains, which are among the most problematic bacterial species in antibiotic development efforts. The superparamagnetic behavior was obtained by synthesizing core iron oxide nanoparticles with a diameter below twenty nm. The MW-assisted hydrothermal method yielded a uniform coating of SPIONs with several sugar ligands, granting strongly negative-charged surfaces, which have eventually contributed to their bactericidal activity. The research work allowed to get insights into the magnetic properties of the sugar ligand coated SPIONs, as well as on morphological and functional characteristics of the hybrid nanoparticles, by employing both spectroscopy and imaging techniques, such as FT-IR, Scanning/Transmission Electron Microscopy (S/TEM). Detailed characterizations of the nanoparticles’ charge, using zeta potential analysis helped to identify the highly charged hybrids for antibacterial applications. Furthermore, studies on the bactericidal properties of selected SL-SPION hybrids highlighted a high selectivity towards both gram-negative and gram-positive bacteria along with improving bactericidal activity of streptomycin/penicillin mixture. Detailed studies done on Pseudomonas aeruginosa revealed that the SPIONs selectively downregulated the virulence factor pyoverdine and altered bacterial morphology depending on the SL chemistry. The synthesized materials with antibacterial activity pave the way for an effective path towards the design and development of nanostructures and coatings against antibiotic-resistant bacterial species.

The Effects of a Varied Gold Shell Thickness on Iron Oxide Nanoparticle Cores in Magnetic Manipulation, T1 and T2 MRI Contrasting, and Magnetic Hyperthermia.

Fe3O4–Au core–shell magnetic-plasmonic nanoparticles are expected to combine both magnetic and light responsivity into a single nanosystem, facilitating combined optical and magnetic-based nanotheranostic (therapeutic and diagnostic) applications, for example, photothermal therapy in conjunction with magnetic resonance imaging (MRI) imaging. To date, the effects of a plasmonic gold shell on an iron oxide nanoparticle core in magnetic-based applications remains largely unexplored. For this study, we quantified the efficacy of magnetic iron oxide cores with various gold shell thicknesses in a number of popular magnetic-based nanotheranostic applications; these included magnetic sorting and targeting (quantifying magnetic manipulability and magnetophoresis), MRI contrasting (quantifying benchtop nuclear magnetic resonance (NMR)-based T1 and T2 relaxivity), and magnetic hyperthermia therapy (quantifying alternating magnetic-field heating). We observed a general decrease in magnetic response and efficacy with an increase of the gold shell thickness, and herein we discuss possible reasons for this reduction. The magnetophoresis speed of iron oxide nanoparticles coated with the thickest gold shell tested here (ca. 42 nm) was only ca. 1% of the non-coated bare magnetic nanoparticle, demonstrating reduced magnetic manipulability. The T1 relaxivity, r1, of the thick gold-shelled magnetic particle was ca. 22% of the purely magnetic counterpart, whereas the T2 relaxivity, r2, was 42%, indicating a reduced MRI contrasting. Lastly, the magnetic hyperthermia heating efficiency (intrinsic loss power parameter) was reduced to ca. 14% for the thickest gold shell. For all applications, the efficiency decayed exponentially with increased gold shell thickness; therefore, if the primary application of the nanostructure is magnetic-based, this work suggests that it is preferable to use a thinner gold shell or higher levels of stimuli to compensate for losses associated with the addition of the gold shell. Moreover, as thinner gold shells have better magnetic properties, have previously demonstrated superior optical properties, and are more economical than thick gold shells, it can be said that “less is more”.

Magnetic separation of nucleic acids from various biological samples using silica-coated iron oxide nanobeads

Magnetic nanobeads can be applied to the magnetic separation of nucleic acids which can be used for diagnosing infectious and genetic diseases of patients. In this study, core-shell structured silica-coated iron oxide (Fe3O4@SiO2) nanobeads with a core size distribution of 40–50 nm and a shell thickness of ∼ 10 nm were synthesized and applied to the magnetic separation of nucleic acids from various biological samples such as cancer cells, viruses, and bacteria. The iron oxide core provided strong superparamagnetic properties with a high saturation magnetization suitable for magnetic separation, and the silica shell provided binding surfaces for nucleic acids. The Fe3O4@SiO2 nanobeads showed the successful magnetic separation performance for all samples.

Co-adsorption of synthetic Mincle agonists and antigen to silica nanoparticles for enhanced vaccine activity: A formulation approach to co-delivery.

To date there is no clinically approved adjuvant to drive a protective T-helper cell 17 (Th17) immune response against Mycobacterium tuberculosis (Mtb). Trehalose Dimycolate (TDM) is a glycolipid molecule found in the cell wall of Mtb and similar species. Our team has discovered novel synthetic TDM derivatives that target Mincle receptors and when presented on the surface of amine functionalized silica nanoparticles (A-SNPs) adopt the requisite supramolecular structure for Mincle receptor agonism. Here we describe the preparation and characterization methods for these critical silica nanoparticles (SNPs) co-loaded with Mincle agonists (MAs) and a model antigen. In this work, A-SNPs with a particle diameter of 246±11nm were prepared and examined for co-adsorption of two synthetic MAs along with ovalbumin (OVA). Due to the insolubility of the studied MAs in aqueous environment, aggregation of the MAs made separation of the adjuvant-loaded A-SNPs from the free-form MAs via centrifugation very challenging. To facilitate separation, we synthesized modified SNPs with comparable amine surface functionalization to the original A-SNPs, but with a superparamagnetic iron oxide core (M-A-SNPs), to allow for magnetic separation. We also substituted Alexa Fluor 488-labeled ovalbumin (AF 488 OVA) for the un-tagged OVA to improve the sensitivity of our quantitation method. A RP-HPLC method was developed to simultaneously determine the amount of adsorption of both the Mincle adjuvant and the model antigen to the A-SNPs. AF488 OVA demonstrated higher than 90% adsorption, with or without the co-adsorption of MAs. Likewise, MAs exhibited higher than 80% adsorption in the presence or absence of antigen. The developed formulations were tested in vitro using murine RAW cells and human peripheral blood mononuclear cells, exhibiting good cytokine induction in both cell lines. Results from these studies indicate that A-SNPs could be used as a customizable presentation platform to co-deliver antigens along with different MAs of varying structural features and biophysical properties.

Stimuli-Responsive Iron Oxide Nanotheranostics: A Versatile and Powerful Approach for Cancer Therapy.

Recent advancements in unravelling elements of cancer biology involved in disease progression and treatment resistance have highlighted the need for a holistic approach to effectively tackle cancer. Stimuli-responsive nanotheranostics based on iron oxide nanoparticles are an emerging class of versatile nanomedicines with powerful capabilities to "seek, sense, and attack" multiple components of solid tumors. In this work, the rationale for using iron oxide nanoparticles and the basic physical principles that impact their function in biomedical applications are reviewed. Subsequently, recent advances in the integration of iron oxide nanoparticles with various stimulus mechanisms to facilitate the development of stimuli-responsive nanotheranostics for application in cancer therapy are summarized. The integration of an iron oxide core with various surface coating mechanisms results in the generation of hybrid nanoconstructs with capabilities to codeliver a wide variety of highly potent anticancer therapeutics and immune modulators. Finally, emerging future directions and considerations for their clinical translation are touched upon.

Highly Fluorescent Doped Fe3O4@C Nanoparticles Cross the Blood–Brain Barrier: Help in Brain Imaging and Blocking the Life Cycle of Mosquitoes

Day by day, humans and animals are infected with life-threatening and deadly diseases due to mosquito bites. Current methods used to fight these diseases are not fully viable and unsafe for humans and animals. Controlling the germ-carrying mosquitoes requires the immediate transfer of a conceptual paradigm. This experiment suggested a safe mosquito control mechanism with fluorescence iron-oxide core carbon-coated (f-Fe3O4@C) nontoxic nanoparticles used as an active agent. As the concept of experiment, we chose mosquitoes of Anopheles, Aedes, and Culex genera because they are found worldwide and infect pathogens. The progression of the life cycle of mosquitoes was observed and imaging under the treated known concentration of f-Fe3O4@C nanoparticles. Resulted that a minimum 3 mg/L and above concentration of f-Fe3O4@C nanoparticles in breeding water these group of larvae can’t attend their adulthood and ultimately died under prolong stay in the larval stage. In this case, though the species can be studied for a sustained time the originality of the wild species is lost.

A novel Citrus sinensis peel ash coated magnetic nanoparticles as an easily recoverable solid catalyst for biodiesel production

A magnetic nano-sized solid catalyst derived from bio-waste Citrus sinensis peel ash (CSPA)@Fe3O4 was developed for the synthesis of biodiesel from waste cooking oil (WCO). The core–shell structure of the catalyst enhanced the surface properties and maintained a controlled size and shape of the catalyst, thus improved the catalyst stability to a great extent. The synthesized catalyst was characterized by several analysis techniques. The high amount of potassium and calcium in the Citrus sinensis peel ash (CSPA) catalyst makes it extremely basic and played an important catalytic role in the transesterification of WCO. The CSPA@Fe3O4 catalyzed transesterification afforded a maximum biodiesel yield of 98% under the optimized reaction conditions such as 6:1 methanol/oil molar ratio, 6 wt% catalyst loading, 65 °C temperature and 3 h time. The activation energy of the reaction was found to be 34. 41 KJ mol−1, which indicated that the transesterification of WCO using the present catalyst is chemically controlled reaction. Beneficially, the magnetic iron oxide core endorsed easily recoverable of the catalyst from the reaction mixtures by using an external magnet. Moreover, the catalyst showed high physical stability and reactivity up to the 9 consecutive cycles, demonstrating it as a promising solid base catalyst for sustainable production of biodiesel.

Polymer-coated magnetic nanoparticles for the efficient capture of Mycobacterium tuberculosis (Mtb)

Modified chitosan and modified poly(styrene-alt-maleic anhydride) (SMA) were synthesized and utilized to coat superparamagnetic magnetite nanoparticles (SPMNs) to act as potential Mycobacterium tuberculosis (Mtb) capturing substrates. Chitosan and SMA were modified to form quaternary derivatives which have the potential to interact with the Mtb cell wall. The nano-substrates were also surface functionalized with a carbohydrate-binding protein, namely Concanavalin A (Con A), which can bind to the Mtb cell wall. Chitosan coated SPMNs were synthesized by in situ co-precipitating Fe2+ and Fe3+ with chitosan followed by further modification. SMA coated SPMNs were synthesized by activating the iron oxide core with 3-aminopropyl(triethoxysilane) followed by further modification. The nano-substrates were evaluated for their affinity and thus capturing capabilities utilizing the mCherry fluorophore tagged bacillus Calmette-Guérin (BCG) strain of Mycobacterium bovis, a live attenuated Mtb-mimic. Quaternary SMA (SMI-qC12) revealed the highest overall affinity for BCG-mCherry (through electrostatic and hydrophobic interactions) whereas Con A immobilized chitosan had the highest affinity for the chitosan coated nanoparticles. The SPMNs were coated with three different polymer loadings and a dilution study was performed to determine the limit of detection. The 0.9 g loaded SMI-qC12 SPMNs revealed the highest affinity for BCG-mCherry as determined via fluorescence microscopy and transmission electron microscopy.

Rare-earth element extraction from geothermal brine using magnetic core-shell nanoparticles-techno-economic analysis

Rare earth elements (REEs) are critical materials having a wide variety of applications such as generating and storing renewable energy. Extracting rare earth metals from geothermal brines is a very challenging problem due to the low concentrations of these elements and engineering challenges with traditional chemical separations methods involving packed sorbent beds or membranes that would impede large volumetric flow rates of geothermal fluids passing through a geothermal power plant. We demonstrate a simple and highly cost-effective nanofluid-based method for extracting rare earth metals from geothermal brines. Core-shell composite nanoparticles that contain a magnetic iron oxide core surrounded by a shell made of metal-organic framework (MOF) sorbent functionalized with chelating ligands were produced to selectively extract rare earth elements. A flowsheet model is used to estimate the capital and operating cost of a potential process to extract Eu from geothermal brines in the Salton Sea area using the magnetic nanofluid technology. The techno-economic analysis (TEA) results show that the annual productivity of Eu from the outlet brine stream of a typical 20 MW geothermal power plant is about 2151 kg. The capital cost to apply the PNNL magnetic nanofluid technology is about $6.8 M and the internal return rate (IRR) for this investment is about 18.1% based on the information collected for the year 2018. Sensitivity analysis has been carried out for some key parameters such as the REE concentration and price and adsorbent cost to reveal their impacts on the IRR.

Superparamagnetic Iron Oxide Nanoparticles Carrying Chemotherapeutics Improve Drug Efficacy in Monolayer and Spheroid Cell Culture by Enabling Active Accumulation.

Cytotoxic and cytostatic chemotherapeutics act by attacking rapidly dividing tumor cells, predominantly affecting malignant tissue and to a certain degree preserving healthy cells. Nonetheless, severe side effects are caused as quickly proliferating healthy cells such as hematopoietic precursors and mucous membranes are impaired as well. This limits the administered dose and eventually allows tumor cells to escape treatment. In order to increase intratumoral drug concentration and simultaneously reduce systemic side effects, nanoparticles have come into focus as drug carriers. The functionalization of superparamagnetic iron oxide nanoparticles (SPIONs) with chemotherapeutics such as mitoxantrone (MTO) enables targeted drug transport by using magnetic forces. Here, we investigate SPIONs consisting of individual iron oxide cores of 10 nm in diameter and a total hydrodynamic diameter of 53 ± 0.8 nm as a transporting system for MTO. Comparing the killing efficacy in monolayer cell culture and multicellular tumor spheroids of HT-29 cells, we show that spheroids tolerate considerably higher doses of nanoparticle-loaded MTO. Therefore, dose predictions from conventional monolayer cell cultures are often misleading for in vivo applications. This was true for both soluble and nanoparticle-bound MTO. Using flow chambers mimicking in vivo blood flow, we furthermore demonstrate that SPIONs can magnetically accumulate MTO. We conclude that SPIONs can function as an effective delivery platform to increase local drug concentrations, thereby potentially overcoming chemotherapy resistance of cells.