Au(III) complexes loaded pH‐responsive magnetic nanogels for cancer therapy

A novel pH‐responsive magnetic nanogels were developed with the aim of targeted delivering and simultaneously releasing of newly synthesized Au(III)‐based anticancer drug, Au(1,7‐Phen)Br₃. The obtained nanogels were characterized by FT‐IR, DLS, EDAX, TEM, XRD, ICP‐Ms and MRI. The TEM images showed that the nanogels had a spherical shape with a mean diameter of 20 nm. The in vitro release studies of Au (III)‐loaded nanogels showed a pH‐triggered controlled release of drugs. The in vitro cytotoxicity assay of samples to human cervical cancer HeLa cell lines indicated that the Au(III)‐loaded magnetic nanogels exert higher cytotoxicity in comparison with free Au(III) complex. Fluorescent microscope images indicated that these magnetic nanogels possessed notable cell specific targeting in vitro in the presence of an external magnetic field. The results show that this superparamagnetic nanocarrier is a promising candidate for inhibiting growth of tumor cells.     

Poly(PEGMA) magnetic nanogels: preparation via photochemical method,characterization and application as drug carrier

One-pot synthesis of magnetic nanogels with excellent biocompatibility via the photochemical method is reported in this paper. Poly(PEGMA) modified superparamagnetic nanogels (poly(PEGMA) magnetic nanogels) were synthesized by in-situ polymerization using poly(ethylene glycol) methacrylate (PEGMA) as the monomer and N, N′-methylene-bis-(acrylamide) (MBA) as the cross-linking agent in magnetite aqueous suspension under UV irradiation. The surface functional groups and components of magnetic nanogels were analyzed by Fourier transform infrared spectroscopy (FTIR) and a thermogravimetric analyzer (TGA). The results indicated that the poly(PEGMA) magnetic nanogels were synthesized successfully by coating poly(PEGMA) on the Fe₃O₄ nanoparticles under UV irradiation, and the Fe₃O₄ nanoparticles content in this nanogels was above 50 wt%. The morphology, size, zeta-potential and magnetic property were also characterized. The magnetic nanogels had a nearly spherical shape and core-shell structure, the average size in aqueous system measured by photon correlation spectroscopy (PCS) was 68.4 nm, which was much bigger than that in the dry state, the nanogels behaved superparamagnetically with saturated magnetization of 58.6 emu/g, and the zeta-potential was −16.3–−17.3 mV at physiological pH (6.8–7.4) which could help to maintain stability in blood. The preliminary application as drug carrier was made and the doxorubicin-loaded magnetic nanogels had an excellent property in slow-release. The experiment indicated that the magnetic nanogel was an ideal candidate carrier in target drug delivery systems and other biomedical application. Supported by the Natural Science Foundation of Shandong Province (Grant No. Q2006F01), Scientific and Technological Project of Shandong Province (Grant No. 2007GG3WZ02066) and Scientific and Technological Project of Department of Education, Shandong (Grant No. J07WC01)     

Synthesis and characterization of PDEAEMA‐based magneto‐nanogels: Preliminary results on the biocompatibility with cells of human peripheral blood

Nanogels based on biocompatible, dual pH‐ and temperature‐sensitive poly(2‐(diethylamino)ethyl) methacrylate (PDEAEMA) have been successfully used as nanocontainers for the encapsulation of magnetite, Fe₃O₄ magnetic nanoparticles (MNPs). For this purpose, citric acid‐coated MNPs were encapsulated into previously synthesized PDEAEMA‐based nanogels using a poly(ethyleneglycol)‐based stabilizer. After the encapsulation of the magnetite MNPs, the so‐called magneto‐nanogels (MNGs) were proved to be multiresponsive on temperature, pH, and magnetic field and colloidally stable. Moreover, preliminary studies on the biocompatibility of these MNGs with cells of human peripheral blood were performed and evidenced quite tolerable biocompatibility, thus suggesting potential use in biomedical applications. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 1479–1494     

Novel approaches for the preparation of magnetic nanogels via covalent bonding

Here, novel methods to encapsulate magnetic nanoparticles (MNPs) into dual‐stimuli‐responsive nanogels via covalent bonding are reported. With the aim of strengthening the attachment of MNPs with the nanogels, primary amine‐ and epoxide‐functionalized stimuli‐sensitive poly(2‐(diethylamino)ethyl methacrylate) (PDEAEMA)‐based nanogels were firstly synthesized. Then, MNPs were incorporated into the nanogels by using different methods, obtaining different families of magnetic nanogels (MNGs). Those MNGs, showing pH‐sensitivity and high superparamagnetic response, could be considered to be widely useful as theranostic agents in biomedical applications. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 3573–3586     

The Synthesis of Magnetic Lysozyme‐Imprinted Polymers by Means of Distillation–Precipitation Polymerization for Selective Protein Enrichment

A protein imprinting approach for the synthesis of core–shell structure nanoparticles with a magnetic core and molecularly imprinted polymer (MIP) shell was developed using a simple distillation–precipitation polymerization method. In this work, Fe₃O₄ magnetic nanoparticles were first synthesized through a solvothermal method and then were conveniently surface‐modified with 3‐(methacryloyloxy)propyltrimethoxylsilane as anchor molecules to donate vinyl groups. Next a high‐density MIP shell was coated onto the surface of the magnetic nanoparticles by the copolymerization of functional monomer acrylamide (AAm), cross‐linking agent N,N′‐methylenebisacrylamide (MBA), the initiator azodiisobutyronitrile (AIBN), and protein in acetonitrile heated at reflux. The morphology, adsorption, and recognition properties of the magnetic molecularly imprinted nanoparticles were investigated by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X‐ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), vibrating sample magnetometer (VSM), and rebinding experiments. The resulting MIP showed a high adsorption capacity (104.8 mg g^?1) and specific recognition (imprinting factor=7.6) to lysozyme (Lyz). The as‐prepared Fe₃O₄@Lyz‐MIP nanoparticles with a mean diameter of 320 nm were coated with an MIP shell that was 20 nm thick, which enabled Fe₃O₄@Lyz‐MIP to easily reach adsorption equilibrium. The high magnetization saturation (40.35 emu g^?1) endows the materials with the convenience of magnetic separation under an external magnetic field and allows them to be subsequently reused. Furthermore, Fe₃O₄@Lyz‐MIP could selectively extract a target protein from real egg‐white samples under an external magnetic field.     

Synthesis of magnetic,reactive, and thermoresponsive Fe3O4 nanoparticles via surface‐initiated RAFT copolymerization of N‐isopropylacrylamide and acrolein

A reversible addition‐fragmentation chain transfer (RAFT) agent was directly anchored onto Fe₃O₄ nanoparticles in a simple procedure using a ligand exchange reaction of S‐1‐dodecyl‐S′‐(α,α′‐dimethyl‐α″‐acetic acid)trithiocarbonate with oleic acid initially present on the surface of pristine Fe₃O₄ nanoparticles. The RAFT agent‐functionalized Fe₃O₄ nanoparticles were then used for the surface‐initiated RAFT copolymerization of N‐isopropylacrylamide and acrolein to fabricate structurally well‐defined hybrid nanoparticles with reactive and thermoresponsive poly(N‐isopropylacrylamide‐co‐acrolein) shell and magnetic Fe₃O₄ core. Evidence of a well‐controlled surface‐initiated RAFT copolymerization was gained from a linear increase of number‐average molecular weight with overall monomer conversions and relatively narrow molecular weight distributions of the copolymers grown from the nanoparticles. The resulting novel magnetic, reactive, and thermoresponsive core‐shell nanoparticles exhibited temperature‐trigged magnetic separation behavior and high ability to immobilize model protein BSA. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 542–550, 2010     

Preparation and characterization of amino-functionalized magnetic nanogels via photopolymerization for MRI applications

To design peptide-targeted iron oxide as magnetic resonance imaging (MRI) contrast agents, amino-functionalized magnetic nanogels were prepared by using N-(2-aminoethyl) methacrylamide hydrochloride (AEM·HCl) as monomer via new photochemical approach. Their chemical structure and composition were characterized by Fourier transform infrared spectra (FTIR) and thermogravimetric analyses (TGA). The core–shell structure of magnetic nanogels was confirmed by high-resolution transmission electron microscopy (HRTEM). The good storage stability, high magnetic content (88.7%), high saturation magnetizations and superparamagnetic behavior suggested their great potentials as MRI contrast agents, which were confirmed by their measurements of r₂ and coronal image of the crossing of mouse kidney.     

Synthesis of Imatinib‐loaded chitosan‐modified magnetic nanoparticles as an anti‐cancer agent for pH responsive targeted drug delivery

Targeted drug delivery is a promising approach to overcome the limitations of classical chemotherapy. In this respect, Imatinib‐loaded chitosan‐modified magnetic nanoparticles were prepared as a pH sensitive system for targeted delivery of drug to tumor sites by applying a magnetic field. The proposed magnetic nanoparticles were prepared through modification of magnetic Fe₃O₄ nanoparticles with chitosan and Imatinib. The structural, morphological and physicochemical properties of the synthesized nanoparticles were determined by different analytical techniques including energy‐dispersive X‐ray spectroscopy (EDS), field emission scanning electron microscopy (FESEM), Fourier‐transform infrared (FTIR) spectroscopy, high resolution transmission electron microscopy (HR‐TEM), vibrating sample magnetometry (VSM), X‐ray diffraction (XRD) and X‐ray photoelectron spectroscopy (XPS). UV/visible spectrophotometry was used to measure the Imatinib contents. Thermal stability of the prepared particles was investigated and their efficiency of drug loading and release profile were evaluated. The results demonstrated that Fe₃O₄@CS acts as a pH responsive nanocarrier in releasing the loaded Imatinib molecules. Furthermore, the Fe₃O₄@CS/Imatinib nanoparticles displayed cytotoxic effect against MCF‐7 breast cancer cells. Results of this study can provide new insights in the development of pH responsive targeted drug delivery systems to overcome the side effects of conventional chemotherapy.     

Synthesis and characterization of pH‐sensitive PAMPS/PVP nanogels in aqueous media

A novel method for preparing poly (2‐acrylamido‐2‐methylpropane sulfonic acid) (PAMPS) and poly (vinylpyrrolidone) (PVP) complex nanogels in PVP aqueous solution is discussed in this paper. The PAMPS/PVP complex nanogels were prepared via polymerization of 2‐acrylamido‐2‐methylpropane sulfonic acid (AMPS) monomer in the presence of PVP nanoparticles which formed in water/acetone cosolvent in presence of N, N′‐methylenebisacrylamide (MBA) as a crosslinker, N, N, N′, N′‐tetramethylethylenediamine (TEMED) and potassium peroxydisulfate (KPS) as redox initiator system. The results of FTIR and ¹H NMR spectra indicated that the compositions of PAMPS/PVP are consistent with the designed structure. TEM micrographs proved that PAMPS/PVP nanogels possess the spherical morphology before and after swelling. These PAMPS/PVP nanogels exhibited pH‐induced phase transition due to protonation of PAMPS chains. The properties of PAMPS/PVP nanogels indicate that PAMPS/PVP nanogels can be developed into a pH‐controlled drug delivery system. Copyright © 2009 John Wiley & Sons, Ltd.     

A Renewable Potentiometric Immunosensor Based on Fe3O4 Nanoparticles Immobilized Anti‐IgG

A renewable potentiometric immunosensor for detection of immunoglobulin G (IgG) has been developed by magnetic force attraction of Fe₃O₄ nanoparticles immobilized goat‐anti‐human IgG antibody. For preparing sensitive film of the sensor, cysteine was bonded on the nano‐Fe₃O₄ particles surface. The cysteine functionalized magnetic nanoparticles was attracted on a solid paraffin carbon paste electrode surface to covalently immobilize of anti‐immunoglobulin G (anti‐IgG) by employing a conventional glutaraldehyde‐crosslinking method. The immunosensor showed a specific response to human immunoglobulin G in the range of 0.1–1.2 ng/mL with a detection limit of 0.023 ng/mL. The immunosensor based on the magnetic nanoparticles was made easily by this method. It can be used expediently, renewed easily and low‐cost relatively. The renewable potentiometric immunosensor with better stability and higher sensitivity can be employed extensively in clinical diagnosis, monitoring of disease and environmental studies and etc.     

Synthesis and self‐assembly of multiple‐responsive magnetic nanogels

In this paper, temperature and pH‐sensitive interpenetrating polymer network (IPN) nanogels (NGs) were firstly prepared, and magnetic hybrid NGs were made through in‐situ precipitation of Fe²⁺ and Fe³⁺ into the IPN NGs. Under the optimized condition, the resulting hybrid NG dispersion with up to 17.3 wt% magnetite was stable, while the size distribution of the NGs is broad due to the formation of Fe₃O₄ nanoparticles outside the NGs. In order to synthesize relatively uniform magnetic NGs, magnetite content was reduced to 8.1 wt% magnetite. The NGs with 8.1 wt% magnetite can quickly self‐assemble into colloidal crystals induced by magnet, while such NGs slowly self‐assembled into colloidal crystals without external magnetic field. Furthermore, the reflection wavelength of the self‐assembled magnetic NGs showed red‐shift with increasing pH and temperature.     

羟丙基-β-环糊精磁性复合微粒的合成及作为阿霉素载体的体外释药研究

羟丙基-β-环糊精因具有内部疏水和外部亲水锥形圆筒空腔结构和良好的生物相容性在磁性药物载体方面有潜在应用价值。本研究将羟丙基-β-环糊精修饰在超顺磁性纳米四氧化三铁粒子表面制备磁性复合微粒,用红外光谱,透射电镜,振动磁强计,电感耦合等离子发射等方法对该复合微粒进行了表征,并将其用于抗肿瘤药物阿霉素的体外载药与释药实验研究。结果表明该复合微粒的粒径大小在10-20nm,饱和磁化强度59.9 emu/g,铁含量55.4%。对阿霉素的载药量为87.8 μg/mg。体外释药结果显示载药复合粒子在PBS中1天,4天,10天的累积释药量分别为35.5%, 49.3%, 76.5%,表明该载体具有一定的药物缓释功能。由此可知,羟丙基-β-环糊精磁性复合微粒可作为磁性靶向给药系统的有效载体。     

Magnetic separation of heavy metal ions and evaluation based on surface‐enhanced Raman spectroscopy: Copper(II) ions as a case study

A new approach was developed for the magnetic separation of copper(II) ions with easy operation and high efficiency. p‐Mercaptobenzoic acid served as the modified tag of Fe₂O₃@Au nanoparticles both for the chelation ligand and Raman reporter. Through the chelation between the copper(II) ions and carboxyl groups on the gold shell, the Fe₂O₃@Au nanoparticles aggregated to form networks that were enriched and separated from the solution by a magnet. A significant decrease in the concentration of copper(II) ions in the supernatant solution was observed. An extremely sensitive method based on surface‐enhanced Raman spectroscopy was employed to detect free copper(II) ions that remained after the magnetic separation, and thus to evaluate the separation efficiency. The results indicated the intensities of the surface‐enhanced Raman spectroscopy bands from p‐mercaptobenzoic acid were dependent on the concentration of copper(II) ions, and the concentration was decreased by several orders of magnitude after the magnetic separation. The present protocol effectively decreased the total amount of heavy metal ions in the solution. This approach opens a potential application in the magnetic separation and highly sensitive detection of heavy metal ions.     

Decoration of Fe3O4 nanoparticles on the surface of poly(acrylic acid) functionalized multi‐walled carbon nanotubes by covalent bonding

Fe₃O₄ nanoparticles were indirectly implanted onto functionalized multi‐walled carbon nanotubes (MWCNTs) leading to a nanocomposite with stronger magnetic performance. Poly(acrylic acid) (PAA) oligomer was first reacted with hydroxyl‐functionalized MWCNTs (MWCNTs‐OH) forming PAA‐grafted MWCNTs (PAA‐g‐MWCNTs). Subsequently, Fe₃O₄ nanoparticles were attached onto the surface of PAA‐g‐MWCNTs through an amidation reaction between the amino groups on the surface of Fe₃O₄ nanoparticles and the carboxyl groups of PAA. Fourier transform infrared spectra confirmed that the Fe₃O₄ nanoparticles and PAA‐g‐MWCNTs were indeed chemically linked. The morphology of the nanocomposites was characterized using transmission electron microscope (TEM). The surface and bulk structure of the nanocomposites were examined using X‐ray diffraction, X‐ray photoelectron spectrometer (XPS), and thermogravimetric analysis (TGA). The magnetic performance was characterized by vibrating sample magnetometer (VSM) and the magnetic saturation value of the magnetic nanocomposites was 47 emu g^?1. The resulting products could be separated from deionized water under an external magnetic field within about 15 s. Finally, the magnetorheological (MR) performances of the synthesized magnetic nanocomposites and pure Fe₃O₄ nanoparticles were examined using a rotational rheometer. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Magnetically Encoded Luminescent Composite Nanoparticles through Layer‐by‐Layer Self‐Assembly

Sensitive and rapid detection of multiple analytes and the collection of components from complex samples are important in fields ranging from bioassays/chemical assays, clinical diagnosis, to environmental monitoring. A convenient strategy for creating magnetically encoded luminescent CdTe@SiO₂@n Fe₃O₄ composite nanoparticles, by using a layer‐by‐layer self‐assembly approach based on electrostatic interactions, is described. Silica‐coated CdTe quantum dots (CdTe@SiO₂) serve as core templates for the deposition of alternating layers of Fe₃O₄ magnetic nanoparticles and poly(dimethyldiallyl ammonium chloride), to construct CdTe@SiO₂@n Fe₃O₄ (n=1, 2, 3, …?) composite nanoparticles with a defined number (n) of Fe₃O₄ layers. Composite nanoparticles were characterized by zeta‐potential analysis, fluorescence spectroscopy, vibrating sample magnetometry, and transmission electron microscopy, which showed that the CdTe@SiO₂@n Fe₃O₄ composite nanoparticles exhibited excellent luminescence properties coupled with well‐defined magnetic responses. To demonstrate the utility of these magnetically encoded nanoparticles for near‐simultaneous detection and separation of multiple components from complex samples, three different fluorescently labeled IgG proteins, as model targets, were identified and collected from a mixture by using the CdTe@SiO₂@n Fe₃O₄ nanoparticles.     

In-situ synthesis of PHEMA magnetic nanogels via photochemical method

One-pot synthesis of magnetic nanogels via photochemical method is reported in this paper. Poly(2-hydroxyethyl methacrylate)(PHEMA) magnetic nanogels are synthesized by in-situ polymerization of 2-hydroxyethyl methacrylate (HEMA) and N,N′-methylene-bis-(acrylamide)(MBA) in Fe₃O₄ aqueous suspension under UV irradiation. The structure and compositions of magnetic nanogels are characterized by FTIR, TGA, SEM, TEM and PCS. TGA measurement indicates that magnetic nanogels contain 90% magnetite. Both naked Fe₃O₄ and magnetic nanogels are superparamagnatic at room temperature according to magnetization curves. The swollen capability of the hydrogel shell is proved by contrasting the particles sizes obtained by SEM, TEM and PCS. Particle diameters can be manipulated by changing monomer concentration and irradiation time. A mechanism of the coating process is proposed. Supported by the Shanghai Municipal Commission for Special Project of Nanometer Science and Technology (Grant No. 0452nm068)     

MnFe2O4 nanoclusters as labels for the quantitative detection of D‐dimer in a lateral‐flow immunochromatographic assay

In this study, MnFe₂O₄ nanoclusters were prepared as bioprobes to establish a lateral‐flow immunochromatographic assay (LFIA) for the rapid and quantitative detection of D‐dimer for the first time. The magnetic properties of the magnetic labels play a key role in the quantitative detection of biomolecules. The 47.3‐nm MnFe₂O₄ magnetic nanoclusters (MNCs) with good dispersion and high saturation magnetization (76 emu/g) were fabricated via thermal decomposition of Fe(acac)₃ with Mn(acac)₂. The prepared MnFe₂O₄ MNCs were well dispersed in water because the surfaces were fully covered with 3,4‐dihydroxyhydrocinnamic acid (DHCA) molecules by ligand exchange. Anti‐D‐dimer antibodies were coupled on the surface of MnFe₂O₄ MNCs, and the target protein, D‐dimer, was detected, in the range 0.05–6 μg/mL. This assay provides a promising platform for D‐dimer detection for point‐of‐care diagnosis.     

Silica aerogel–poly(ethylene‐co‐vinyl acetate) composite for transparent heat retention films

Poly(ethylene‐co‐vinyl acetate) (EVA) plastic films are widely used for solar coverings including photovoltaic modules and commercial greenhouse films, but are poor at controlling heat flow. In this work, silica aerogel (SA) nanogels were examined for preparing transparent heat retention EVA films that block far infrared spectra radiation to maintain heat, without compromising the optical performance of the films. SA nanogels were melt‐mixed using a mini twin‐screw extruder with EVA pellets to form SA/EVA composite, which were pressed into thin films with controlled thickness. The composite films were characterized in terms of optical properties using a variety of analytical methods including FTIR, UV–Vis spectroscopy, electron, confocal, and atomic force microscopy. Both thermicity and thermal conductivity of commercial and experimental SA/EVA films were measured. The results demonstrated that the SA/EVA films gave improved infrared retention compared to commercial thermal plastic films without compromising visible light transmission, showing the potential for this approach in next generation heat retention films. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2014 , 52, 927–935     

Separation and detection of multiple pathogens in a food matrix by magnetic SERS nanoprobes

A rapid and sensitive method was developed here for separation and detection of multiple pathogens in food matrix by magnetic surface-enhanced Raman scattering (SERS) nanoprobes. Silica-coated magnetic probes (MNPs@SiO₂) of ∼100 nm in diameter were first prepared via the reverse microemulsion method using cetyltrimethylammonium bromide as a surfactant and tetraethyl orthosilicate as the silica precursor. The as-prepared MNPs@SiO₂ were functionalized with specific pathogen antibodies to first capture threat agents directly from a food matrix followed by detection using an optical approach enabled by SERS. In this scheme, pathogens were first immuno-magnetically captured with MNPs@SiO₂, and pathogen-specific SERS probes (gold nanoparticles integrated with a Raman reporter) were functionalized with corresponding antibodies to allow the formation of a sandwich assay to complete the sensor module for the detection of multiple pathogens in selected food matrices, just changing the kinds of Raman reporters on SERS probes. Here, up to two key pathogens, Salmonella enterica serovar Typhimurium and Staphylococcus aureus, were selected as a model to illustrate the probability of this scheme for multiple pathogens detection. The lowest cell concentration detected in spinach solution was 10³ CFU/mL. A blind test conducted in peanut butter validated the limit of detection as 10³ CFU/mL with high specificity, demonstrating the potential of this approach in complex matrices.     

A Novel Magnetism‐assisted Electrochemical Immunosensor with Sub‐Picomolar Sensitivity

A novel electrochemical immunosensor based on a magnetic glassy carbon electrode (MGCE) was developed for the quantitative determination of human immunoglobulin G (IgG). The immunosensing interface was fabricated by initially depositing silver nanoparticles on the MGCE surface and then immobilizing anti‐human IgG antibodies via the magnetic force between MGCE and Fe₃O₄ nanoparticles. The antibodies were covalently bonded to the amine‐functionalized Fe₃O₄ nanoparticles. Under optimal conditions, the magnetism‐assisted immunosensor exhibited a wide linear range from 0.1 pg/mL to 1.0 µg/mL with the detection limit of 0.05 pg/mL. Furthermore, the immunosensor displayed the advantages of good reproducibility and satisfactory stability.