Iron Oxide Core Research Articles

Magnetic targeting combined with active targeting of dual-ligand iron oxide nanoprobes to promote the penetration depth in tumors for effective magnetic resonance imaging and hyperthermia

The combination of multi-targeting magnetic nanoprobes and multi-targeting strategies has potential to facilitate magnetic resonance imaging (MRI) and magnetic induction hyperthermia of the tumor. Although the thermo-agents based on magnetic iron oxide nanoparticles (MION) have been successfully used in the form of intratumoral injection in clinical cure of glioblastoma, the tumor-targeted thermotherapy by intravenous administration remains challenging. Herein, we constructed a c(RGDyK)- and d-glucosamine-grafted bispecific molecular nanoprobe (Fe3O4@RGD@GLU) with a magnetic iron oxide core of size 22.17 nm and a biocompatible shell of DSPE-PEG2000, which can specially target the tumor vessel and cancer cells. The selection of c(RGDyK) could make the nanoprobe enter the neovascularization endotheliocyte through αvβ3-mediated endocytosis, which drastically reduced the dependence on the enhanced permeability and retention (EPR) effect in tumor. This dual-ligand nanoprobe exhibited strong magnetic properties and favorable biocompatibility. In vitro studies confirmed the anti-phagocytosis ability against macrophages and the specific targeting capability of Fe3O4@RGD@GLU. Then, the imaging effect and anti-tumor efficacy were compared using different targeting strategies with untargeted nanoprobes, dual-targeted nanoprobes, and magnetic targeting combined with dual-targeted nanoprobes. Moreover, the combination strategy of magnetic targeting and active targeting promoted the penetration depth of nanoprobes in addition to the increased accumulation in tumor tissue. Thus, the dual-targeted magnetic nanoprobe together with the combined targeting strategy could be a promising method in tumor imaging and hyperthermia through in vivo delivery of theranostic agents. Statement of SignificanceMagnetic induction hyperthermia based on iron oxide nanoparticles has been used in clinic for adjuvant treatment of recurrent glioblastoma. Nonetheless, this application is limited to intratumoral injection, and tumor-targeted hyperthermia by intravenous injection remains challenging. In this study, we developed a multi-targeted strategy by combining magnetic targeting with active targeting of dual-ligand magnetic nanoprobes. This combination mode acquired optimum contrast imaging effect through MRI and tumor-suppressive effect through hyperthermia under an alternating current magnetic field. The design of the nanoprobe was suitable for targeting most tumor lesions, which enabled it to be an effective theranostic agent with extensive uses. This study showed significant enhancement of the penetration depth and accumulation of nanoprobes in the tumor tissue for efficient imaging and hyperthermia.

Cross-Linked Polystyrene Shells Grown on Iron Oxide Nanoparticles via Surface-Grafted AGET-ATRP in Microemulsion.

Most applications of nanoparticles require robust stabilization, for example, by surface-bound ligands or the encapsulation within polymer shells. Furthermore, for biomedical applications, the particles must be dispersible in a complex biological environment. Thus, high-quality nanoparticles synthesized in organic solvents must be transferred into aqueous media. Here, we present a novel scalable method enabling the robust hydrophilic encapsulation of non-agglomerated nanoparticles by growing polystyrene shells via AGET-ATRP in microemulsion. To demonstrate this approach, we encapsulate iron oxide nanoparticles (diameter: 13.7 ± 0.6 nm). Because the ATRP initiator is grafted onto the nanoparticles' surface, the shells are covalently attached to the iron oxide cores. By varying the amount of monomers, the shell thickness can be adjusted precisely, as indicated by the increasing hydrodynamic size from ∼22 to 26 nm (DLS, number mean) with an increasing amount of added monomers. Moreover, the degree of cross-linking can be controlled by the amount of added divinylbenzene (DVB). To evaluate the robustness of the polymer shells against ion infusion, we introduce a novel colorimetric method, which is based on the formation of the red iron thiocyanate complex. After addition of HCl, the increase in absorbance at 468 nm indicates leaching of iron ions from the polymer-encapsulated core particles. These measurements confirm that with increasing shell thickness, significantly improved shielding is achieved. Furthermore, high concentrations of added DVB [33-50% (v/v) in a monomer mixture] improve the shielding effect. However, when smaller amounts of DVB were added [10-25% (v/v)], the shielding effect was diminished, even in comparison to non-cross-linked polymer shells. This finding suggests a higher porosity of shells with a low degree of cross-linking.

Preparation and Characterization of Spion-CDs as a Multifunctional Fluorescence/Magnetic Resonance Nanoparticle

Abstract A multifunctional nanoparticle, Super Paramagnetic Iron Oxide Nanoparticle-Carbon Dots (SPION-CDs), for fluorescence and magnetic resonance imaging is introduced. This nanoparticle possesses the magnetic properties of super-paramagnetic iron oxide (SPION) core as well as the fluorescence characteristics of carbon dots (CDs) coated in mesoporous structure. The SPION-CDs were synthesized using a high temperature facile single-pot hydrothermal method. The products were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray diffraction (XRD), UV/vis absorption, vibrating sample magnetometer (VSM). The cytotoxic effect of SPION-CDs on OVCAR-3 cells was also evaluated. The synthesized nanoparticle possesses optimal size, low toxicity and excellent magnetic properties, including super-paramagnetic behavior (Ms = 42 emu g−1). Moreover, in the viewpoint of optical properties, the quantum yield of ~2.4% was obtained and the nanoparticle shows good fluorescence stability for cell-labeling studies. This multifunctional nanoparticle with appropriate characterization is a promising candidate for multimodal fluorescence/magnetic resonance imaging platform.

Graphene Oxide-Based Nanostructured DNA Sensor.

Quick detection of DNA sequence is vital for many fields, especially, early-stage diagnosis. Here, we develop a graphene oxide-based fluorescence quenching sensor to quickly and accurately detect small amounts of a single strand of DNA. In this paper, fluorescent magnetic nanoparticles (FMNPs) modified with target DNA sequence (DNA-t) were bound onto the modified graphene oxide acting as the fluorescence quenching element. FMNPs are made of iron oxide (Fe3O4) core and fluorescent silica (SiO2) shell. The average particle size of FMNPs was 74 ± 6 nm and the average thickness of the silica shell, estimated from TEM results, was 30 ± 4 nm. The photoluminescence and magnetic properties of FMNPs have been investigated. Target oligonucleotide (DNA-t) was conjugated onto FMNPs through glutaraldehyde crosslinking. Meanwhile, graphene oxide (GO) nanosheets were produced by a modified Hummers method. A complementary oligonucleotide (DNA-c) was designed to interact with GO. In the presence of GO-modified with DNA-c, the fluorescence intensity of FMNPs modified with DNA-t was quenched through a FRET quenching mechanism. Our study indicates that FMNPs can not only act as a FRET donor, but also enhance the sensor accuracy by magnetically separating the sensing system from free DNA and non-hybridized GO. Results indicate that this sensing system is ideal to detect small amounts of DNA-t with limitation detection at 0.12 µM.

Theranostic Nanoparticles for RNA-Based Cancer Treatment.

Certain genetic mutations lead to the development of cancer through unchecked cell growth and division. Cancer is typically treated through surgical resection, radiotherapy, and small-molecule chemotherapy. A relatively recent approach to cancer therapy involves the use of a natural process wherein small RNA molecules regulate gene expression in a pathway known as RNA interference (RNAi). RNA oligomers pair with a network of proteins to form an RNA-induced silencing complex, which inhibits the translation of mRNA into proteins, thereby controlling the expression of gene products. Synthetically produced RNA oligomers may be designed to target and silence specific oncogenes to provide cancer therapy. The primary challenges facing the use of the RNAi pathway for cancer therapy are the safe and efficacious delivery of RNA payloads and their release at pertinent sites within disease-causing cells. Nucleases are abundant in the bloodstream and intracellular environment, and therapeutic RNA sequences often require a suitable carrier to provide protection from degradation prior to reaching their site of action in the body. The use of metal core nanoparticles (NPs) serving as targeted delivery vehicles able to shield and direct RNA payloads to their intended destinations have recently gained favor. Biological barriers present in the body establish a size prerequisite for drug delivery vehicles; to overcome recognition by the body's immune system and to gain access to intracellular environments, drug carriers must be small (< 100 nm). Iron oxide and gold core NPs can be synthesized with a high degree of control to create uniform ultrasmall drug delivery vehicles capable of bypassing key biological barriers. While progress is being made in size control of liposomal and polymer NPs, such advances still lag in comparison to the exquisite tunability and time stability of size engineering achievable with metal core NPs at bulk scales. Further, unlike lipid- and viral-based transfection agents, the biodistribution of metal core NPs can be traced using noninvasive imaging techniques that capitalize on the interaction of electromagnetic radiation and the inorganic atoms at the core of the NPs. Finally, metal core NPs have been shown to match the transfection efficiency of conventional RNA-delivery vehicles while also providing less immunogenicity and minimal side effects through the addition of tumor-targeting ligands on their surface. This Account reviews recent advances in the use of iron oxide and gold NPs for RNAi therapy. An overview of the different types of RNA-based therapies is provided along with a discussion of the advantages and current limitations of the technique. We highlight design considerations for the use of iron oxide and gold NP carriers in RNAi, including a discussion of the importance of size and its role in traversing biological barriers, NP surface modifications required for targeted delivery and RNA payload release, and auxiliary properties supporting imaging functionality for treatment monitoring. Applications of NPs for combination therapies including the pairing of RNAi with chemotherapy, photothermal therapy, immunotherapy, and radiotherapy are explored through examples. Finally, future perspectives are provided with a focus on the current limitations and the potential for clinical translation of iron oxide and gold NPs in RNAi therapy.

Multifunctional motion-to-color janus transducers for the rapid detection of sepsis biomarkers in whole blood

Self-propelled particles are revolutionizing sensing applications thanks to a unique motion-based signal generation mechanism in which biorecognition reactions are detected as changes in the velocity of the colloids. Here a new family of self-propelled multifunctional Janus particles is introduced that enables detecting changes in particle motion colorimetrically. The particles consist of an iron oxide core that provides color and magnetism, and a Janus coating that provides biospecific recognition and locomotive properties. In this approach, biomolecular interactions trigger changes in particle motion that are detected as variations in color when spotted on a piece of paper. These variations in color are then read and quantified with a custom-made smartphone app. The high surface area and magnetism of the particles makes them ideal building blocks for developing biosensors because they allow for the rapid capture of a target molecule and the removal of non-specific interactions. Biosensors engineered with the proposed multifunctional particles were able to detect the sepsis biomarker procalcitonin at clinically relevant concentrations within 13 min in whole blood, which is faster than other approaches requiring hour-long incubation steps under controlled conditions to detect the same biomarker in purified serum. The short assay time along with the point-of-need design makes these biosensors suitable for stratifying patients according to their sepsis risk level during triage independently of resource constraints.

Scavenging of reactive oxygen species by phenolic compound-modified maghemite nanoparticles.

Maghemite (γ-Fe2O3) nanoparticles obtained through co-precipitation and oxidation were coated with heparin (Hep) to yield γ-Fe2O3@Hep, and subsequently with chitosan that was modified with different phenolic compounds, including gallic acid (CS-G), hydroquinone (CS-H), and phloroglucinol (CS-P), to yield γ-Fe2O3@Hep-CS-G, γ-Fe2O3@Hep-CS-H, and γ-Fe2O3@Hep-CS-P particles, respectively. Surface modification of the particles was analyzed by transmission electron microscopy, dynamic light scattering, attenuated total reflection Fourier transform infrared spectroscopy, and thermogravimetric analysis. Magnetic measurements indicated that the polymer coating does not affect the superparamagnetic character of the iron oxide core. However, magnetic saturation decreased with increasing thickness of the polymer coating. The antioxidant properties of the nanoparticles were analyzed using a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Cellular uptake and intracellular antioxidant activity of the particles were evaluated by an iron assay and flow cytometry, respectively, using L-929 and LN-229 cells. Compared to the control, the phenolic modification significantly reduced intracellular reactive oxygen species (ROS) levels to 35–56%, which was associated with a 6–8-times higher cellular uptake in L-929 cells and a 21–31-times higher cellular uptake in LN-229 cells. In contrast, γ-Fe2O3@Hep particles induced a 3.8-times and 14.9-times higher cellular uptake without inducing antioxidant activity. In conclusion, the high cellular uptake and the antioxidant properties associated with the phenolic moieties in the modified particles allow for a potential application in biomedical areas.

Mesoporous electromagnetic composite particles: Electric current responsive release of biologically active molecules and antibacterial properties

Electric current responsive magnetic composite particles are prepared in three steps. In the first step, spherical and mesoporous submicrometer-sized magnetic iron oxide (Fe3O4) core particles are prepared by solvothermal method. Then magnetic Fe3O4 particles are functionalized with amine groups using glycine, where the COO- group of glycine formed a bridging bidentate interaction with the hydroxyl groups on Fe3O4 particle surface. Finally polyaniline (PAni) is grafted onto the functional Fe3O4 surface via in situ seeded chemical oxidative polymerization of aniline. The average size of Fe3O4/PAni composite particles is 418.82 nm with mesoporous surface structure. Electron microscopic images confirmed that PAni pockets are localized on the surface of Fe3O4 core particles. The surface composition is further confirmed by Fourier transform IR (FTIR), X-ray photoelectron spectroscopy (XPS) and thermogravimety (TG) analyses. Fe3O4/PAni composite particles possessed strong paramagnetic property (47.77 emu g−1). The electrical conductivity of Fe3O4/PAni composite particles (1.46 × 10-4 S cm−1) remained in the same order of magnitude as that of reference PAni particles (3.42 × 10-4 S cm−1). The release behavior of biologically active molecules such as trypsin (TR), albumin (AL) and p-acetamido phenol (pAP) is studied using low intensity electric current as stimuli to prevent degradation. Depending on the nature, up to ˜ 33–88% of adsorbed biomolecules/drug are released from the electromagnetic Fe3O4/PAni composite particles. Compared to Fe3O4 particles, Fe3O4/PAni composite particles exhibited moderate antibacterial property.

Colloids or powders: Which nanoparticle formulations do cells like more?

Understanding the difference in physicochemical properties and biological response between colloidal and powder formulations of identical materials is important before the given materials are used in a medical milieu. In this study we compared a set of biological effects of colloidal and powder formulations of composite nanoparticles comprising superparamagnetic iron oxide cores and silicate/carbon shells. Magnetic dipole interaction between adjacent nanoparticles was more pronounced in their powders than in their colloidal formulations. Nanoparticles delivered as powders were thus more responsive to the magnetic field, but exhibited reduced uptake in bone and brain cancer cells, including K7M2 osteosarcoma line and U87 and E297 glioblastoma lines. Specifically, while the alternate magnetic field elicited a more rapid heat generation in cell culture media supplemented with the magnetic powders, the nanoparticles dispersed in the same media were uptaken by the cancer cells more copiously. The cellular uptake proved to be more crucial in defining the effect on cell survival, given that suspended formulations elicited a greater degree of cancer cell death in the magnetic field compared to the powder-containing formulations. Because of this effect, colloidal formulations were able to target cancer cells more effectively than the powders: they reduced the viability of all three tested cancer cell lines to a significantly greater degree that the viability of the normal, MDCK-MDR1 cell line. It is concluded that better uptake profile can make up for the lower heating rate in the AC field and lead to a more effective magnetic hyperthermia therapy. These results also demonstrate that the direct delivery of ferrofluids is more optimal than the administration of their constitutive particles as powders.

Composite Nanoparticles Based on the Lexan Polymer Matrix, Ytterbium Complexes of Porphyrins, and Iron Oxide for NIR Luminescent Diagnostics and Neoplasm Theranostics

The synthesis procedure and the spectral luminescent properties of nanoparticles containing the ytterbium complex of protoporphyrin IX dimethyl ester in a Lexan-based polymer matrix, promising for application in neoplasm diagnostics, are described. Nanoparticles have an increased luminescence lifetime in the 700–1100 nm near infrared region and almost no porphyrin free base fluorescence in the red spectral region, which shows promise in using the nanoparticles for diagnostic purposes. For theranostic purposes, the synthesis of multifunctional nanoparticles with a core of iron oxides and a Lexan-polymer shell containing the ytterbium complex of hematoporphyrin IX tetramethyl ester was carried out. We assume iron oxide nanoparticles are responsible for the local hyperthermia procedure.

Design Principles for Thermoresponsive Core-Shell Nanoparticles: Controlling Thermal Transitions by Brush Morphology.

In this feature article, we summarize our recent work on understanding and controlling the thermal behavior of nanoparticles grafted with thermoresponsive polymer shells. Precision synthesis of monodisperse superparamagnetic iron oxide nanocrystals was combined with irreversible dense grafting of nitrodopamide-anchored thermoresponsive polymer chains. We provide an overview of how the dense and stable grafting of biomedically relevant polymers, including poly(ethylene glycol), poly(N-isopropylacrylamide), polysarcosin, and polyoxazolines, can be achieved. This platform has made it possible for us to demonstrate that the polymer brush geometry, as defined by the nanoparticle core and relative polymer brush size, determines the thermal transitions of the polymer brush. We furthermore summarize our work on how the polymer shell transitions and nanoparticle aggregation can be tuned. With the independent variation of the core and the shell, we can optimize and precisely control the thermally controlled solubility of our system. Finally, our feature article gives examples relevant to current and future applications. We show how the thermal response of the shell influences the nanoparticle performance in biological fluids and interactions with proteins and cells, also under purely magnetic actuation of the nanoparticles through the superparamagnetic iron oxide core.

Design of hybrid protein-coated magnetic core-mesoporous silica shell nanocomposites for MRI and drug release assessed in a 3D tumor cell model

In this work, we describe the design and the use of a novel theranostic hybrid nanocomposite made of an iron oxide core and a mesoporous silica shell (IO@MS) of ca. 30 nm coated by human serum albumin (HSA) layer for magnetic resonance imaging and drug delivery applications. The porosity of IO@MS nanoparticles was loaded with an antitumoral drug, Doxorubicin (Dox) reaching a high drug loading capacity (DLC) of 34 w%. To entrap the drug, a tight HSA coating held via isobutyramide (IBAM) binders was deposited. We show that this protein nanoassembly entraps the drugs efficiently and behaves as an innovative enzyme-sensitive gatekeeper that is degraded upon protease action. Finally we assess the Dox release in a 3D cell model via confocal imaging and its cytotoxicity is shown by growth inhibition studies on liver cancer cell spheroids.

Polypseudorotaxane functionalized magnetic nanoparticles as a dual responsive carrier for roxithromycin delivery

A magnetic-pH dual responsive drug delivery system was prepared for antibacterial therapy to reduce the side effects on nonpathological cells or tissues. Iron oxide (Fe3O4) core was surface-functionalized with silane coupling agents to link β‑cyclodextrin (β-CD) (CDMNP), and a polypseudorotaxanes shell where polyethyleneglycol chains threaded much CD molecules was further prepared on the magnetic Fe3O4 core (CDMNP-PEG-CD) to enhance loading capacity of roxithromycin (ROX). CDMNP-PEG-CD with a hydrodynamic diameter of ~168 nm was cytocompatible, superparamagnetic, magnetic-responsive and stable for 180 min of storage. No significant interaction with serum albumin was shown for the nanocomposites. The in vitro release from ROX-loaded CDMNP-PEG-CD nanocomposites was about 76% of total drug within 30 min at pH 1.0, 1.6-fold of that at pH 7.4 and 2-fold of that at pH 8.0, presenting pH-responsive drug release behaviors. The nanocomposites showed positive antibacterial activity against both E. coli and S. aureus based on an agar diffusion method. The antibacterial activity of the nanocomposites was more sensitive against E. coli than S. aureus, and the inhibition halo against E. coli was 85% more than that of Fe3O4. CDMNP-PEG-CD nanocomposites allowed for the localization and fast concentration of hydrophobic drugs, providing a broad potential range of therapeutic applications.

Crystalline-Amorphous Permalloy@Iron Oxide Core-Shell Nanoparticles Decorated on Graphene as High-Efficiency, Lightweight, and Hydrophobic Microwave Absorbents.

The exploration of high-efficiency microwave absorption materials with lightweight and hydrophobic features is highly expected to reduce or eliminate the electromagnetic pollution. Graphene-based nanocomposites are universally acknowledged as promising candidates for absorbing microwaves due to their remarkable dielectric properties and lightweight characteristic. However, the hydrophilicity of graphene may reduce their stability and restrict the applications in moist environment. Herein, a well-designed heterostructure composed of crystalline permalloy core and amorphous iron oxide shell was uniformly adhered on oleylamine-modified graphene nanosheets by a one-pot thermal decomposition method. Compared with the recognized hydrophilic graphene-based hybrid materials, the permalloy@iron oxide/graphene nanocomposites show excellent hydrophobic and water-resistant features with a water contact angle of 136.5°. Besides, the nanocomposites show high-efficiency microwave absorption performance, benefiting from the tunneling effect, polarization, interface interaction, impedance matching condition, and synergistic effect between core-shell permalloy@iron oxide nanoparticles and graphene nanosheets. A broad effective absorption bandwidth with reflection loss (RL) value exceeding -10 dB can be obtained from 4.25 to 18 GHz, covering about 86% measured frequency range when the absorber thickness is 2.0-5.0 mm. Also, the microwave absorption performance of nanocomposites can be tuned by changing the amount of graphene. More importantly, a greatly improved microwave absorption effectiveness of -71.1 dB can be achieved for the nanocomposites in comparison with the bare permalloy@iron oxide nanoparticles (-5.6 dB) and oleylamine-modified GO nanosheets (-3.56 dB). The lightweight and hydrophobic permalloy@iron oxide/graphene nanocomposites with high-efficiency microwave absorption performance are highly promising to improve the environmental adaptability of electric devices, especially in the wet environment.

Dextran-Coated Iron Oxide Nanoparticles as Biomimetic Catalysts for Localized and pH-Activated Biofilm Disruption.

Biofilms are surface-attached bacterial communities embedded within an extracellular matrix that create localized and protected microenvironments. Acidogenic oral biofilms can demineralize the enamel-apatite on teeth, causing dental caries (tooth decay). Current antimicrobials have low efficacy and do not target the protective matrix and acidic pH within the biofilm. Recently, catalytic nanoparticles were shown to disrupt biofilms but lacked a stabilizing coating required for clinical applications. Here, we report dextran-coated iron oxide nanoparticles termed nanozymes (Dex-NZM) that display strong catalytic (peroxidase-like) activity at acidic pH values, target biofilms with high specificity, and prevent severe caries without impacting surrounding oral tissues in vivo. Nanoparticle formulations were synthesized with dextran coatings (molecular weights from 1.5 to 40 kDa were used), and their catalytic performance and bioactivity were assessed. We found that 10 kDa dextran coating provided maximal catalytic activity, biofilm uptake, and antibiofilm properties. Mechanistic studies indicated that iron oxide cores are the source of catalytic activity, whereas dextran on the nanoparticle surface provided stability without blocking catalysis. Dextran-coating facilitated NZM incorporation into exopolysaccharides (EPS) structure and binding within biofilms, which activated hydrogen peroxide (H2O2) for localized bacterial killing and EPS-matrix breakdown. Surprisingly, dextran coating enhanced selectivity toward biofilms while avoiding binding to gingival cells. Furthermore, Dex-NZM/H2O2 treatment significantly reduced the onset and severity of caries lesions (vs control or either Dex-NZM or H2O2 alone) without adverse effects on gingival tissues or oral microbiota diversity in vivo. Therefore, dextran-coated nanozymes have potential as an alternative treatment to control tooth decay and possibly other biofilm-associated diseases.

Effect of superparamagnetic nanoparticles coated with various electric charges on α-synuclein and β-amyloid proteins fibrillation process.

BackgroundMost of nanoparticles are nontoxic and have high absorption capability. Therefore, nanoparticles binding can effectively restrain fibrillation of β-amyloid and α-synuclein proteins and eventually prevent the toxicity of pathogenesis peptide of Alzheimer. Super paramagnetic iron oxide nanoparticles (SPIONs) contain iron oxide core which can be connected to a special part through magnetic coating.Materials and methodsIn this study, the effect of SPIONs with different charges was simultaneously examined on the fibrillation of both β-amyloid and α-synuclein proteins by applying Thioflavin-T assay.ResultsAccording to the results of the investigation on amyloid-fibrillation mechanism in both β-amyloids and α-synucleins, it was revealed that negatively-charged nanoparticles encoded to –COOH by dextran-coating were able to have a considerable absorption decrease from 17,000–12,000 after 320 minutes delay to lag phase and decrease in binding level of thioflavin-T particles to β-sheets.ConclusionThe different concentrations of these nanoparticles and special coating of each particle had an effect on the kinetics of β-amyloid and α-synuclein fibrillations.

Step-by-Step Protocol for Superparamagnetic Nanoparticle-Based Plasma Membrane Isolation from Eukaryotic Cell.

Here, we elaborate our detailed protocol for synthesis, functionalization, and application of superparamagnetic nanoparticle (SPMNP) for plasma membrane and lysosome isolation. We used standard thermal decomposition-based synthesis of iron oxide (Fe3O4) core SPMNP 1.0. Using ligand addition methodology, we surface functionalized SPMNP 1.0 with phospholipids and generated phospholipid-SPMNP 2.0. Further we used NH2-phospholipid-SPMNP 2.0 to isolate plasma membrane. Using our SPMNP subcellular fractionation protocol, we are able to isolate high-pure-high-yield plasma membrane using NH2-phospholipid-SPMNP 2.0. As a future perspective, we propose to use SPMNP on clinical patient samples and perform mass spectrometry-based proteomics, lipidomics, and glycomics for early cancer diagnosis.

Step-by-Step Protocol for Superparamagnetic Nanoparticle-Based Endosome and Lysosome Isolation from Eukaryotic Cell.

Here, we report our step-by-step protocol for superparamagnetic nanoparticle (SPMNP)-based endosome and lysosome isolation from HeLa. Briefly, we synthesized SPMNP 1.0 with iron oxide (Fe3O4) core using thermal decomposition method. Further, we performed ligand-exchange strategy for surface functionalization of SPMNP 1.0 with dimercaptosuccinic acid (DMSA). Thus, we generated DMSA-SPMNP 2.0 and used DMSA-SPMNP 2.0 to isolate endosomes and lysosome from HeLa cells. Using our SPMNP subcellular fractionation protocol, we are able to isolate high-pure-high-yield lysosomes using DMSA-SPMNP 2.0 for lysosome proteomics and lipidomics in order to better understand subcellular compartments.

Modified core-shell magnetic mesoporous zirconia nanoparticles formed through a facile "outside-to-inside" way for CT/MRI dual-modal imaging and magnetic targeting cancer chemotherapy.

Iron oxide based magnetic nanoparticles (MNPs) as typical theranostic nanoagents have been popularly used in various biomedical applications. Conventional core–shell MNPs are usually synthesized from inside to outside. This method has strict requirements on the interface properties of magnetic cores and the precursors of the coating shell. The shape and size of MNPs are significantly influenced by that of the pre-synthesized magnetic cores. Most core–shell MNPs have only single T2W MRI imaging ability. Herein, we propose a new synthetic strategy for core-mesoporous shell structural MNPs, where hollow mesoporous nanospheres which exhibit an intrinsic property for both CT imaging and drug loading were used as the shell and the magnetic cores were produced in the cavity of the shell. A new type of MNPs, Fe3O4@ZrO2 nanoparticles (M-MZNs), were developed using this facile outside-to-inside way, where multiple Fe3O4 nanoparticles grew inside the cavity of the mesoporous hollow ZrO2 nanospheres through chemical coprecipitation. The obtained MNPs not only exhibited superior magnetic properties and CT/MR imaging ability but also high drug loading capacity. In vitro experiment results revealed that M-MZNs-PEG loaded with doxorubicin (DOX) presented selective growth inhibition against cancer cells due to pH-sensitive DOX release and enhanced endocytosis by cancer cells under a magnetic field. Furthermore, the proposed MNPs exhibited CT/MRI dual modal imaging ability and effective physical targeting to tumor sites in vivo. More importantly, experiments of magnetic targeting chemotherapy on tumor bearing mice demonstrated that the nanocomposites significantly suppressed tumor growth without obvious pathological damage to major organs. Henceforth, this study provides a new strategy for CT/MRI dual-modal imaging guided and magnetic targeting cancer therapy.

Synthesis and Characterization of Bi-Functional Poly (Acrylic Acid-Co-2-hydroxyethylmethacrylate) Coated Iron Oxide Magnetic Composite Particles

This paper covers the targetable magnetic iron oxide core and biodegradable, cost-effective, eco-friendly polymer shell considering their versatile and extensive use in various fields. In this work, poly (acrylic acid–co-2-hydroxyethylmethacrylate) [P (AA-co-HEMA)] magnetic composite polymer particles were synthesized by the method of two-stage solution polymerization in aqueous media. At first synthesis, the Fe3O4 particles by a traditional co-precipitation method and in the second stage occurs the formation of the polymer using acrylic acid (AA) as monomer and 2-hydroxyethyl methacrylate (HEMA) as co-monomer. Finally, the synthesized iron oxide particles encapsulated by a polymer to modify the surface of composite particles. The modified composite particles were then characterized by Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffractometry (XRD), Dynamic Light Scattering (DLS), Thermo Gravimetric Analysis (TGA) and Vibrating Sample Magnetometry (VSM). The existence of carboxyl (-COOH) & hydroxyl (-OH) groups in the composite particles was confirmed by FTIR. XRD indicated the crystalline cubic spinel structure of magnetic composite particles. VSM results showed that the synthesized coated composite particles were paramagnetic in nature magnetic saturation is obtained 72.72 emu/g and 97.9 emu/g for bare Fe3O4 and coated magnetic composite particles respectively.