Iron Oxide Core Research Articles

Development and bioevaluation of controlled release 5-aminoisoquinoline nanocomposite: a synergistic anticancer activity against human colon cancer

<abstract> <p>The current study presents a bimodal therapeutic platform for cancer treatment. Bimodal implies that the presented drug loaded core-shell structure is capable of elevating the tumor tissue temperature (hyperthermia) through the superparamagnetic iron oxide core and simultaneously release a Poly (ADP-ribose) polymerase-1(PARP-1)-modifying agent from the thermoresponsive shell. Magnetic thermoresponsive nanocomposite MTN was synthesized via an in situ free radical polymerization of thermo-responsive (N-isopropylacrylamide) (NIPAAm) monomer in the presence of 11-nm monodisperse SPIONs. The composite was allowed to swell in various concentrations of the PARP inhibitor: 5-aminoisoquinoline (5-AIQ) forming drug-loaded magnetic thermoresponsive nanocomposite (MTN-5.AIQ). Structural characterization of the formed composite is studied via various experimental tools. To assess the coil to globule transition temperature, the lower critical solution temperature (LCST) is determined by differential scanning calorimetry (DSC) method and the cloud point (Tp) is determined by turbidometry. Magnetic thermoresponsive nanocomposite (MTN) is formed with excellent potential for hyperthermia. A high drug loading efficiency (85.72%) is obtained with convenient temperature dependent drug release kinetics. Biocompatibility and cytotoxic efficacy are tested on an in vivo and in vitro colorectal-adenocarcinoma model, respectively. MTN.5-AIQ administration exhibits normal hepatic and renal functions as well as lower toxic effect on normal tissue. In addition, the composite effectively inhibits Caco-2 cells viability upon incubation. Based on the obtained results, the proposed therapeutic platform can be considered as a novel, promising candidate for dual therapy of colorectal adenocarcinoma exhibiting a PARP-1 overexpression. as well as increased the inhabiting efficacy of 5-AIQ.</p> </abstract>

Laparoscopic Probe for Sentinel Lymph Node Harvesting Using Magnetic Nanoparticles.

Sentinel lymph node harvesting is an essential step in the surgical treatment of a growing number of malignancies. Various techniques are available to facilitate this purpose. The present study reports a new laparoscopic technique for lymph node harvesting using magnetic nanoparticles containing a superparamagnetic iron-oxide core and dextran coating. This study assesses the clinical relevance of the prototype and provides input for further technological development on the way to clinical implementation. A laparoscopic differential magnetometer prototype was built, utilizing a nonlinear detection principle (differential magnetometry) for magnetic identification of lymph nodes. The iron content sensitivity, depth & spatial sensitivity, and angular sensitivity were analyzed to investigate clinical options. The minimum detectable amount of iron was 9.8 μg at a distance of 1 mm. The detection depth was 5, 8, and 10 mm for samples containing 126, 252, and 504 μg iron, respectively. The maximum lateral detection distance was 5, 7, and 8 mm for samples containing 126, 252, and 504 μg iron, respectively. A sample containing 504 μg iron was detectable at all angulations assessed (0°, 30°, 60° and 90°). The laparoscopic differential magnetometer demonstrates promising results for further investigation and development towards laparoscopic lymph node harvesting using magnetic nanoparticles. The laparoscopic differential magnetometer facilitates a novel method for sentinel lymph node harvesting, which helps to determine prognosis and treatment of cancer patients.

Hedgehog-inspired magnetic nanoparticles for effectively capturing and detecting exosomes

Exosomes, as one type of extracellular vesicle derived from multiple cells, have much potential as cancer biomarkers in clinical applications, but their enrichment and detection remain a huge challenge. Herein, inspired by the burr-like structure of the hedgehog, we present a new nanoparticle with a nanoneedle-assembled shell and a magnetic core for the effective capture and detection of exosomes. The unique nanoneedle structures endowed the magnetic nanoparticles with a large surface area for antibody modification so that the nanoparticles could serve as a platform for efficient exosome capture. In addition, the controllable movement of exosome-combined nanoparticles, which is due to the magnetic iron oxide cores, provides tremendous convenience for separating exosomes. The practical value of these nanoparticles in exosome analyses of serum from healthy patients and patients with liver cancer has also been demonstrated. Thus, we believe that bioinspired hierarchical nanoparticles are promising for biomedical and clinical applications.

Core-Shell Fe2O3@La1-xSrxFeO3-δ Material for Catalytic Oxidations: Coverage of Iron Oxide Core, Oxygen Storage Capacity and Reactivity of Surface Oxygens.

A series of Fe2O3@LSF (La0.8Sr0.2FeO3−δ perovskite) core-shell materials (CSM) was prepared by infiltration of LSF precursors gel containing various complexants and their mixtures to nanocrystalline aggregates of hematite followed by thermal treatment. The content of LSF phase and amount of carboxyl groups in complexant determine the percent coverage of iron oxide core with the LSF shell. The most conformal coating core-shell material was prepared with citric acid as the complexant, contained 60 wt% LSF with 98% core coverage. The morphology of the CSM was studied by HRTEM-EELS combined with SEM-FIB for particles cross-sections. The reactivity of surface oxygen species and their amounts were determined by H2-TPR, TGA-DTG, the oxidation state of surface oxygen ions by XPS. It was found that at complete core coverage with perovskite shell, the distribution of surface oxygen species according to redox reactivity in CSM resemble pure LSF, but its lattice oxygen storage capacity is 2–2.5 times higher. At partial coverage, the distribution of surface oxygen species according to redox reactivity resembles that in iron oxide.

Cyclodextrin-Appended Superparamagnetic Iron Oxide Nanoparticles as Cholesterol-Mopping Agents.

Cholesterol plays a crucial role in major cardiovascular and neurodegenerative diseases, including Alzheimer’s disease and rare genetic disorders showing altered cholesterol metabolism. Cyclodextrins (CDs) have shown promising therapeutic efficacy based on their capacity to sequester and mobilise cholesterol. However, the administration of monomeric CDs suffers from several drawbacks due to their lack of specificity and poor pharmacokinetics. We present core-shell superparamagnetic iron oxide nanoparticles (SPIONs) functionalised with CDs appended to poly (2-methyl-2-oxazoline) polymers grafted in a dense brush to the iron oxide core. The CD-decorated nanoparticles (CySPIONs) are designed so that the macrocycle is specifically cleaved off the nanoparticle’s shell at a slightly acidic pH. In the intended use, free monomeric CDs will then mobilise cholesterol out of the lysosome to the cytosol and beyond through the formation of an inclusion complex. Hence, its suitability as a therapeutic platform to remove cholesterol in the lysosomal compartment. Synthesis and full characterization of the polymer as well as of the core-shell SPION are presented. Cholesterol-binding activity is shown through an enzymatic assay.

SiO2 based nanocomposite for simultaneous magnetic removal and discrimination of small pollutants in water

A nanocomposite adsorbent material was synthetized in order to obtain an efficient system able to remove, by means of chemical adsorption, mainly aromatic analytes dissolved in aqueous phase. The adsorbing substrate is composed by a magnetic responsive iron oxide (γ-Fe2O3) core coated by a shell of SiO2. The adsorption process is mediated by the chemical interaction among amine and silanol groups on the surface of the nanocomposite adsorbent and the analyte π cloud. The paramagnetic core allows to remove the formed nanosystem-analyte adduct quickly and completely, representing a huge improvement in comparison of the most used gravimetric separation. The removal efficiency obtained using the proposed nanocomposite reaches about 93% for the dangerous pollutant 1,2-phenylenediamine in water solution, 70% for dinitrophenol, 60% for aniline. Further, the nano-adsorbent was decorated with plasmonic Ag nanoparticles without significantly affecting the ability to adsorb the aromatic compounds. The presence of the plasmonic nanoparticles on the SiO2 surface allows to obtain surface enhanced Raman scattering (SERS) of the signals of the adsorbed aniline and 1,2-phenylenediamine proposing this approach to remove and, concomitantly, discriminate the retrieved pollutants from water.

Novel magnetic organic\u2013inorganic hybrids based on aromatic polyamides and ZnFe2O4 nanoparticles with biological activity

Magnetic nanoparticles were creatively selected as stable, inexpensive, biodegradable, facile recoverable, and functionalizable supports for a variety of synthetic and natural polymers. Herein, for the first time, aromatic polyamide was synthesized on the magnetic core of zinc iron oxide (ZnFe2O4). Terephthaloyl chloride and derivations of phenylenediamine were employed as monomers in this polymerization process. The toxicity of the synthesized hybrid at the highest concentration (1000 μg/ml) is 13.65% and on the other hand, the cell viability percentage is 86.35%. So, the prepared hybrid is biocompatible and non-toxic to Hu02 cells. Also, it has antibacterial ability against gram-positive and gram-negative bacteria. Because the results show that the minimum inhibitory concentration (MIC) of the synthesized polymer for bacteria such as Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 27853 is in the range of 500–1000 µg/ml. Moreover, the hemolytic effect of ZnFe2O4 based hybrid was below 9% at the concentration of 1000 μg/ml. Therefore, it is compatible with red blood cells.

Enhanced Li-ion diffusion and electrochemical performance in strained-manganese-iron oxide core-shell nanoparticles.

Efforts to improve energy storage depend greatly on the development of efficient electrode materials. Recently, strain has been employed as an alternate approach to improve ion mobility. While lattice strain has been well-researched in catalytic applications, its effects on electrochemical energy storage are largely limited to computational studies due to complexities associated with strain control in nanomaterials as well as loss of strain due to the phase change of the active material during charging-discharging. In this work, we overcome these challenges and investigate the effects of strain on supercapacitor performance in Li-ion-based energy devices. We synthesize epitaxial Fe3O4@MnFe2O4 (core@shell) nanoparticles with varying shell thickness to control the lattice strain. A narrow voltage window for electrochemical testing is used to limit the storage mechanism to lithiation-delithiation, preventing a phase change and maintaining structural strain. Cyclic voltammetry reveals a pseudocapacitive behavior and similar levels of surface charge storage in both strained- and unstrained-MnFe2O4 samples; however, diffusive charge storage in the strained sample is twice as high as the unstrained sample. The strained-MnFe2O4 electrode exceeds the performance of the unstrained-MnFe2O4 electrode in energy density by ∼33%, power density by ∼28%, and specific capacitance by ∼48%. Density functional theory shows lower formation energies for Li-intercalation and lower activation barrier for Li-diffusion in strained-MnFe2O4, corresponding to a threefold increase in the diffusion coefficient. The enhanced Li-ion diffusion rate in the strained-electrodes is further confirmed using the galvanostatic intermittent titration technique. This work provides a starting pointto using strain engineering as a novel approach for designing high performance energy storage devices.

Design and fabrication of hybrid triple-responsive κ-carrageenan-based nanospheres for controlled drug delivery

In the last two decades, the utilization of magnetic nanospheres in intelligent polymeric structures have received increased attention of researchers in numerous biomedical applications. Here, hybrid nanostructured triple-responsive magnetic nanospheres (κ-Car-g-P(AA/DMA)@Fe3O4) containing inorganic iron oxide core (Fe3O4) and organic graft copolymeric shell based on κ-carrageenan (κ-Car) and poly(acrylic acid/dimethylaminoethyl methacrylate) (P(AA/DMA)) were synthesized by microwave induced co-precipitation technique. The structure, size, surface morphology, magnetic property and stability of synthesized κ-Car-g-P(AA/DMA)@Fe3O4 magnetic nanospheres were characterized using FTIR, UV, XRD, TEM, Zeta-sizer, and VSM. κ-Car-g-P(AA/DMA)@Fe3O4 nanospheres were loaded with 5-Fluorouracil (5-FU) as an antineoplastic drug, and their 5-FU release behavior was explored in diverse graft yields, pH values, temperatures and in the existence of an alternating magnetic field. The κ-Car-g-P(AA/DMA)@Fe3O4 nanospheres demonstrated pH-, thermo-, and magnetic field-responsive 5-FU release with good biocompatibility and excellent anticancer activity. In addition, 5-FU release under 50 mT magnetic field reached to 100% within 4 h. This work exhibits that hybrid nanospheres have a triple stimuli-responsive influence, which is of principal importance for the future design and application of multi-functional responsive platforms to develop externally stimulated release of active agents and their healthcare capability.

Iron oxide nanoparticle targeted chemo-immunotherapy for triple negative breast cancer

Triple negative breast cancer (TNBC) is difficult to treat effectively, due to its aggressiveness, drug resistance, and lack of the receptors required for hormonal therapy, particularly at the metastatic stage. Here, we report the development and evaluation of a multifunctional nanoparticle formulation containing an iron oxide core that can deliver doxorubicin, a cytotoxic agent, and polyinosinic:polycytidylic acid (Poly IC), a TLR3 agonist, in a targeted and simultaneous fashion to both breast cancer and dendritic cells. Endoglin-binding peptide (EBP) is used to target both TNBC cells and vasculature endothelium. The nanoparticle demonstrates favorable physicochemical properties and a tumor-specific targeting profile. The nanoparticle induces tumor apoptosis through multiple mechanisms including direct tumor cell killing, dendritic cell-initiated innate and T cell-mediated adaptive immune responses. The nanoparticle markedly inhibits tumor growth and metastasis and substantially extends survival in an aggressive and drug-resistant metastatic mouse model of TNBC. This study points to a promising platform that may substantially improve the therapeutic efficacy for treating metastatic TNBC.

Development of Dextran-Coated Magnetic Nanoparticles Loaded with Protocatechuic Acid for Vascular Inflammation Therapy.

Vascular inflammation plays a crucial role in the progression of various pathologies, including atherosclerosis (AS), and thus it has become an attractive therapeutic target. The protocatechuic acid (PCA), one of the main metabolites of complex polyphenols, is endowed with anti-inflammatory activity, but its formulation into nanocarriers may increase its bioavailability. In this study, we developed and characterized dextran shell‒iron oxide core nanoparticles loaded with PCA (MNP-Dex/PCA) and assessed their cytotoxicity and anti-inflammatory potential on cells acting as key players in the onset and progression of AS, namely, endothelial cells (EC) and monocytes/macrophages. The results showed that MNP-Dex/PCA exert an anti-inflammatory activity at non-cytotoxic and therapeutically relevant concentrations of PCA (350 μM) as supported by the reduced levels of inflammatory molecules such as MCP-1, IL-1β, TNF-α, IL-6, and CCR2 in activated EC and M1-type macrophages and functional monocyte adhesion assay. The anti-inflammatory effect of MNP-Dex/PCA was associated with the reduction in the levels of ERK1/2 and p38-α mitogen-activated protein kinases (MAPKs) and NF-kB transcription factor. Our data support the further development of dextran shell-magnetic core nanoparticles as theranostic nanoparticles for guidance, imaging, and therapy of vascular inflammation using PCA or other anti-inflammatory compounds.

Alpha-ketoglutarate decorated iron oxide-gold core-shell nanoparticles for active mitochondrial targeting and radiosensitization enhancement in hepatocellular carcinoma

The ability of some tumours to impart radioresistance serves as a barrier in the cancer therapeutics. Mitochondrial metabolism significantly persuades this cancer cell survival, incursion and plays a crucial role in conferring radioresistance. It would be of great importance to target the active mitochondria to overcome this resistance and achieve tumoricidal efficacy. The current report investigates the improved radiosensitization effect (under Gamma irradiation) in hepatocellular carcinoma through active mitochondrial targeting of alpha-ketoglutarate decorated iron oxide-gold core-shell nanoparticles (GNP). The loading of a chemotherapeutic drug N-(4-hydroxyphenyl)retinamide in GNP allows adjuvant chemotherapy, which further sensitizes cancerous cells for radiotherapy. The GNP shows a drug loading efficiency of 8.5 wt% with a sustained drug release kinetics. The X-Ray diffraction (XRD) pattern and High-Resolution Transmission Electron microscopy (HRTEM) indicates the synthesis of core iron oxide nanoparticles with indications of a thin layer of gold shell on the surface with 1:7 ratios of Fe: Au. The GNP application significantly reduced per cent cell viability in Hepatocellular carcinoma cells through improved radiosensitization at 5 Gy gamma radiation dose. The molecular mechanism revealed a sharp increment in reactive oxygen species (ROS) generation and DNA fragmentation. The mitochondrial targeting probes confirm the presence of GNP in the mitochondria, which could be the possible reason for such improved cellular damage. In addition to the active mitochondrial targeting, the currently fabricated nanoparticles work as a potent Magnetic Resonance Imaging (MRI)/Computed Tomography (CT) contrast agent. This multifunctional therapeutic potential makes GNP as one of the most promising theragnostic molecules in cancer therapeutics.

Core Cross-Linked Polymeric Micelles for Specific Iron Delivery: Inducing Sterile Inflammation in Macrophages.

Iron is an essential co-factor for cellular processes. In the immune system, it can activate macrophages and represents a potential therapeutic for various diseases. To specifically deliver iron to macrophages, iron oxide nanoparticles are embedded in polymeric micelles of reactive polysarcosine-block-poly(S-ethylsulfonyl-l-cysteine). Upon surface functionalization via dihydrolipoic acid, iron oxide cores act as crosslinker themselves and undergo chemoselective disulfide bond formation with the surrounding poly(S-ethylsulfonyl-l-cysteine) block, yielding glutathione-responsive core cross-linked polymeric micelles (CCPMs). When applied to primary murine and human macrophages, these nanoparticles display preferential uptake, sustained intracellular iron release, and induce a strong inflammatory response. This response is also demonstrated in vivo when nanoparticles are intratracheally administered to wild-type C57Bl/6N mice. Most importantly, the controlled release concept to deliver iron oxide in redox-responsive CCPMs induces significantly stronger macrophage activation than any other iron source at identical iron levels (e.g., Feraheme), directing to a new class of immune therapeutics.

The Use of Iron Oxide Nanoparticles to Reprogram Macrophage Responses and the Immunological Tumor Microenvironment.

The synthesis and functionalization of iron oxide nanoparticles (IONPs) is versatile, which has enhanced the interest in studying them as theranostic agents over recent years. As IONPs begin to be used for different biomedical applications, it is important to know how they affect the immune system and its different cell types, especially their interaction with the macrophages that are involved in their clearance. How immune cells respond to therapeutic interventions can condition the systemic and local tissue response, and hence, the final therapeutic outcome. Thus, it is fundamental to understand the effects that IONPs have on the immune response, especially in cancer immunotherapy. The biological effects of IONPs may be the result of intrinsic features of their iron oxide core, inducing reactive oxygen species (ROS) and modulating intracellular redox and iron metabolism. Alternatively, their effects are driven by the nanoparticle coating, for example, through cell membrane receptor engagement. Indeed, exploiting these properties of IONPs could lead to the development of innovative therapies. In this review, after a presentation of the elements that make up the tumor immunological microenvironment, we will review and discuss what is currently known about the immunomodulatory mechanisms triggered by IONPs, mainly focusing on macrophage polarization and reprogramming. Consequently, we will discuss the implications of these findings in the context of plausible therapeutic scenarios for cancer immunotherapy.

An iron oxide nanoparticle-based transdermal nanoplatform for dual-modal imaging-guided chemo-photothermal therapy of superficial tumors

Transdermal delivery is an attractive strategy for treating superficial tumors. However, the applications of existing transdermal systems have been limited by low transdermal efficiency and poor therapeutic outcomes. Here, we develop a transdermal nanoplatform (+)T-SiDs, based on superparamagnetic iron oxide core, surface-modified with cationic lipids, transdermal enhanced peptide TD, and 1,1’-dioctadecyl-3,3,3’,3’-tetramethylindotricarbocyanine iodide (DiR), and loaded with doxorubicin. The (+)T-SiDs compositions enable MR/NIR dual-modal imaging guided synergistic chemo-photothermal therapy to superficial tumors treatment via transdermal delivery. The (+)T-SiDs exhibit good stability, efficient cellular uptake, pH/photothermal responsive drug release, and high photothermal conversion efficiency (47.45%). Importantly, the transdermal delivery of (+)T-SiDs is significantly enhanced by TD functionalization. In vivo MR/NIR imaging shows that the (+)T-SiDs exhibit high transdermal efficiency and specificity in localization to the tumor site. Moreover, in comparison with individual chemo- or photothermal therapies, the combination of chemo-photothermal therapy exhibits more efficient tumor inhibition effects. This work presents a new transdermal treatment nanoplatform for dual-modal imaging-guided chemo-photothermal therapy of superficial tumors, with efficient tumor eradication and low systemic toxicity thus offering strong potential for clinical adoption. Statement of significanceTransdermal delivery is an attractive strategy for treating superficial tumors. However, a highly efficient transdermal nanoplatform remains to be developed. Herein, we designed a multifunctional transdermal nanoplatform for dual-modal imaging-guided chemo-photothermal therapy of superficial tumors, comprised of a super-paramagnetic iron oxide (SPIO) nanoparticle, which can act as an MRI contrast agent and photothermal agent; a transdermal enhanced peptide (TD) and cationic lipids, which can accelerate skin penetration; and a NIR dye (DiR) and doxorubicin (DOX), which can achieve a synergistic enhanced chemo-photothermal therapy with NIR imaging ability. The transdermal nanoplatform achieved efficient tumor eradication and low systemic toxicity, thus offering strong potential for clinical adoption.

In vitro cellular activity of maghemite/cerium oxide magnetic nanoparticles with antioxidant properties

Magnetic γ-Fe2O3/CeO2 nanoparticles were obtained by precipitation of Ce(NO3)3 with ammonia in the presence of γ-Fe2O3 seeds. The formation of CeO2 nanoparticles on the seeds was confirmed by transmission electron microscopy linked with selected area electron diffraction, energy-dispersive X-ray spectroscopy, electron energy loss spectroscopy, and dynamic light scattering. The γ-Fe2O3/CeO2 particle surface was functionalized with PEG-neridronate to improve the colloidal stability in PBS and biocompatibility. Chemical and in vitro biological assays proved that the nanoparticles, due to the presence of cerium oxide, effectively scavenged radicals, thus decreasing oxidative stress in the model cell line. PEG functionalization of the nanoparticles diminished their in vitro aggregation and facilitated lysosomal cargo degradation in cancer cells during autophagy, which resulted in concentration-dependent cytotoxicity of the nanoparticles. Finally, the iron oxide core allowed easy magnetic separation of the particles from liquid media and may enable monitoring of nanoparticle biodistribution in organisms using magnetic resonance imaging.

Condensed Clustered Iron Oxides for Ultrahigh Photothermal Conversion and In Vivo Multimodal Imaging.

Magnetic iron oxide nanocrystals (MIONs) are established as potent theranostic nanoplatforms due to their biocompatibility and the multifunctionality of their spin-active atomic framework. Recent insights have also unveiled their attractive near-infrared photothermal properties, which are, however, limited by their low near-infrared absorbance, resulting in noncompetitive photothermal conversion efficiencies (PCEs). Herein, we report on the dramatically improved photothermal conversion of condensed clustered MIONs, reaching an ultrahigh PCE of 71% at 808 nm, surpassing the so-far MION-based photothermal agents and even benchmark near-infrared photothermal nanomaterials. Moreover, their surface passivation is achieved through a simple self-assembly process, securing high colloidal stability and structural integrity in complex biological media. The bifunctional polymeric canopy simultaneously provided binding sites for anchoring additional cargo, such as a strong near-infrared-absorbing and fluorescent dye, enabling in vivo optical and photoacoustic imaging in deep tissues, while the iron oxide core ensures detection by magnetic resonance imaging. In vitro studies also highlighted a synergy-amplified photothermal effect that significantly reduces the viability of A549 cancer cells upon 808 nm laser irradiation. Integration of such-previously elusive-photophysical properties with simple and cost-effective nanoengineering through self-assembly represents a significant step toward sophisticated nanotheranostics, with great potential in the field of nanomedicine.

A Detailed Investigation of the Onion Structure of Exchanged Coupled Magnetic Fe3-δO4@CoFe2O4@Fe3-δO4 Nanoparticles.

Nanoparticles that combine several magnetic phases offer wide perspectives for cutting edge applications because of the high modularity of their magnetic properties. Besides the addition of the magnetic characteristics intrinsic to each phase, the interface that results from core-shell and, further, from onion structures leads to synergistic properties such as magnetic exchange coupling. Such a phenomenon is of high interest to overcome the superparamagnetic limit of iron oxide nanoparticles which hampers potential applications such as data storage or sensors. In this manuscript, we report on the design of nanoparticles with an onion-like structure which has been scarcely reported yet. These nanoparticles consist of a Fe3-δO4 core covered by a first shell of CoFe2O4 and a second shell of Fe3-δO4, e.g., a Fe3-δO4@CoFe2O4@Fe3-δO4 onion-like structure. They were synthesized through a multistep seed-mediated growth approach which consists consists in performing three successive thermal decomposition of metal complexes in a high-boiling-point solvent (about 300 °C). Although TEM micrographs clearly show the growth of each shell from the iron oxide core, core sizes and shell thicknesses markedly differ from what is suggested by the size increasing. We investigated very precisely the structure of nanoparticles in performing high resolution (scanning) TEM imaging and geometrical phase analysis (GPA). The chemical composition and spatial distribution of atoms were studied by electron energy loss spectroscopy (EELS) mapping and spectroscopy. The chemical environment and oxidation state of cations were investigated by 57Fe Mössbauer spectrometry, soft X-ray absorption spectroscopy (XAS) and X-ray magnetic circular dichroism (XMCD). The combination of these techniques allowed us to estimate the increase of Fe2+ content in the iron oxide core of the core@shell structure and the increase of the cobalt ferrite shell thickness in the core@shell@shell one, whereas the iron oxide shell appears to be much thinner than expected. Thus, the modification of the chemical composition as well as the size of the Fe3-δO4 core and the thickness of the cobalt ferrite shell have a high impact on the magnetic properties. Furthermore, the growth of the iron oxide shell also markedly modifies the magnetic properties of the core-shell nanoparticles, thus demonstrating the high potential of onion-like nanoparticles to accurately tune the magnetic properties of nanoparticles according to the desired applications.

Specific detection of Staphylococcus aureus infection and marker for Alzheimer disease by surface enhanced Raman spectroscopy using silver and gold nanoparticle-coated magnetic polystyrene beads

Targeted and effective therapy of diseases demands utilization of rapid methods of identification of the given markers. Surface enhanced Raman spectroscopy (SERS) in conjunction with streptavidin–biotin complex is a promising alternative to culture or PCR based methods used for such purposes. Many biotinylated antibodies are available on the market and so this system offers a powerful tool for many analytical applications. Here, we present a very fast and easy-to-use procedure for preparation of streptavidin coated magnetic polystyrene–Au (or Ag) nanocomposite particles as efficient substrate for surface SERS purposes. As a precursor for the preparation of SERS active and magnetically separable composite, commercially available streptavidin coated polystyrene (PS) microparticles with a magnetic core were utilized. These composites of PS particles with silver or gold nanoparticles were prepared by reducing Au(III) or Ag(I) ions using ascorbic acid or dopamine. The choice of the reducing agent influences the morphology and the size of the prepared Ag or Au particles (15–100 nm). The prepare composites were also characterized by HR-TEM images, mapping of elements and also magnetization measurements. The content of Au and Ag was determined by AAS analysis. The synthesized composites have a significantly lower density against magnetic composites based on iron oxides, which considerably decreases the tendency to sedimentation. The polystyrene shell on a magnetic iron oxide core also pronouncedly reduces the inclination to particle aggregation. Moreover, the preparation and purification of this SERS substrate takes only a few minutes. The PS composite with thorny Au particles with the size of approximately 100 nm prepared was utilized for specific and selective detection of Staphylococcus aureus infection in joint knee fluid (PJI) and tau protein (marker for Alzheimer disease).

Cytotoxicity of Methotrexate Conjugated to Glycerol Phosphate Modified Superparamagnetic Iron Oxide Nanoparticles.

A systematic study was carried out to evaluate the uptake and cytotoxicity of methotrexate (MTX) conjugated to superparamagnetic iron oxide nanoparticles (SPIONs) modified with glycerol phosphate (Glyc) and phosphorylethanolamine (PEA), using MCF-7 cancer cell line as model. The ligand shell composition was controlled in such a way to get SPIONs with nine different surface functionalization and up to three co-conjugated ligands but the very iron oxide core, in order to test and compare uptake and cytotoxicity, and verify possible additive effects. Folic acid (FA), the non-toxic analogue of MTX, was also explored as ligand for SPIONs. Glyc was shown to enhance dramatically the cellular uptake despite the high negative zeta potentials, whereas PEA, FA and MTX was found to have a much lower effect on the cellular uptake. Also, a significant ten times lowering of IC50 was observed for the co-conjugated MTX in the SPION-Glyc/PEA/MTX as compared to the free drug, whereas the analogue SPION-Glyc/PEA/FA nanoparticles exhibited no significant cytotoxicity. In short, the conjugation of MTX to SPIONs enhanced dramatically its cytotoxicity and decreased the IC50 value against MCF-7 tumor cells as compared to the free drug, probably due to the enhanced uptake of SPIONs as a result of their surface modification with Glyc/PEA, demonstrating that SPION-Glyc/PEA is a good nanocarrier for co-conjugated methotrexate.