Fluorescence-tagged amphiphilic brush copolymer encapsulated Gd2O3 core-shell nanostructures for enhanced T 1 contrast effect and fluorescent imaging.

To obtain suitable T 1 contrast agents for magnetic resonance imaging (MRI) application, aqueous Gd2O3 nanoparticles (NPs) with high longitudinal relativity (r 1) are demanded. High quality Gd2O3 NPs are usually synthesized through a non-hydrolytic route which requires post-synthetic modification to render the NPs water soluble. The current challenge is to obtain aqueous Gd2O3 NPs with high colloidal stability and enhanced r 1 relaxivity. To overcome this challenge, fluorescence-tagged amphiphilic brush copolymer (AFCP) encapsulated Gd2O3 NPs were proposed as suitable T 1 contrast agents. Such a coating layer provided (i) superior aqueous stability, (ii) biocompatibility, as well as (iii) multi-modality (conjugation with fluorescence dye). The polymeric coating layer thickness was simply adjusted by varying the phase-transfer parameters. By reducing the coating thickness, i.e. the distance between the paramagnetic centre and surrounding water protons, the r 1 relaxivity could be enhanced. In contrast, a thicker polymeric layer coating prevents Gd(3+) ions leakage, thus improving its biocompatibility. Therefore, it is important to strike a balance between the biocompatibility and the r 1 relaxivity behaviour. Lastly, by conjugating fluorescence moiety, an additional imaging modality was enabled, as demonstrated from the cell-labelling experiment.

Synthesis of manganese ferrite/graphene oxide nanocomposites for biomedical applications.

In this study, MnFe(2)O(4) nanoparticle (MFNP)-decorated graphene oxide nanocomposites (MGONCs) are prepared through a simple mini-emulsion and solvent evaporation process. It is demonstrated that the loading of magnetic nanocrystals can be tuned by varying the ratio of graphene oxide/magnetic nanoparticles. On top of that, the hydrodynamic size range of the obtained nanocomposites can be optimized by varying the sonication time during the emulsion process. By fine-tuning the sonication time, MGONCs as small as 56.8 ± 1.1 nm, 55.0 ± 0.6 nm and 56.2 ± 0.4 nm loaded with 6 nm, 11 nm, and 14 nm MFNPs, respectively, are successfully fabricated. In order to improve the colloidal stability of MGONCs in physiological solutions (e.g., phosphate buffered saline or PBS solution), MGONCs are further conjugated with polyethylene glycol (PEG). Heating by exposing MGONCs samples to an alternating magnetic field (AMF) show that the obtained nanocomposites are efficient hyperthermia agents. At concentrations as low as 0.1 mg Fe mL(-1) and under an 59.99 kA m(-1) field, the highest specific absorption rate (SAR) recorded is 1588.83 W g(-1) for MGONCs loaded with 14 nm MFNPs. It is also demonstrated that MGONCs are promising as magnetic resonance imaging (MRI) T(2) contrast agents. A T(2) relaxivity value (r(2) ) as high as 256.2 (mM Fe)(-1) s(-1) could be achieved with MGONCs loaded with 14 nm MFNPs. The cytotoxicity results show that PEGylated MGONCs exhibit an excellent biocompatibility that is suitable for biomedical applications.

Supramolecular Surface Functionalization of Iron Oxide Nanoparticles with α-Cyclodextrin-Based Cationic Star Polymer for Magnetically-Enhanced Gene Delivery.

Supramolecular polymers formed through host-guest complexation have inspired many interesting developments of functional materials for biological and biomedical applications. Here, we report a novel design of a non-viral gene delivery system composed of a cationic star polymer forming supramolecular complexes with the surface oleyl groups of superparamagnetic iron oxide nanoparticles (SPIONs), for magnetically enhanced delivery of DNA into mammalian cells. The cationic star polymer was synthesized by grafting multiple oligoethylenimine (OEI) chains onto an α-cyclodextrin (α-CD) core. The SPIONs were synthesized from iron(III) acetylacetonate and stabilized by hydrophobic oleic acid and oleylamine in hexane, which were characterized in terms of their size, structure, morphology, and magnetic properties. The synthesized magnetic particles were found to be superparamagnetic, making them a suitable ferrofluid for biological applications. In order to change the hydrophobic surface of the SPIONs to a hydrophilic surface with functionalities for plasmid DNA (pDNA) binding and gene delivery, a non-traditional but simple supramolecular surface modification process was used. The α-CD-OEI cationic star polymer was dissolved in water and then mixed with the SPIONs stabilized in hexane. The SPIONs were "pulled" into the water phase through the formation of supramolecular host-guest inclusion complexes between the α-CD unit and the oleyl surface of the SPIONs, while the surface of the SPIONs was changed to OEI cationic polymers. The α-CD-OEI-SPION complex could effectively bind and condense pDNA to form α-CD-OEI-SPION/pDNA polyplex nanoparticles at the size of ca. 200 nm suitable for delivery of genes into cells through endocytosis. The cytotoxicity of the α-CD-OEI-SPION complex was also found to be lower than high-molecular-weight polyethylenimine, which was widely studied previously as a standard non-viral gene vector. When gene transfection was carried out in the presence of an external magnetic field, the α-CD-OEI-SPION/pDNA polyplex nanoparticles greatly increased the gene transfection efficiency by nearly tenfold. Therefore, the study has demonstrated a facile two-in-one method to make the SPIONs water-soluble as well as functionalized for enhanced magnetofection.

GO-Functionalized Large Magnetic Iron Oxide Nanoparticles with Enhanced Colloidal Stability and Hyperthermia Performance.

Because of their high magnetization and suitable biocompatibility, iron-oxide nanoparticles (IONPs) have been widely employed in various biomedical applications, including magnetic hyperthermia for cancer treatment. In many cases, the colloidal stability requirement will limit the usage of ferromagnetic particles that are usually associated with good magnetic response. To address this challenge, a stable carrier for better colloidal stability regardless of the size or shape of the IONPs while at the same time providing enhanced magnetic hyperthermia heating performance is required. In this work, IONPs of different sizes (4, 8, 20, 45, and 250 nm) were engineered to reside in the graphene oxide (GO) sheet carrier, which were stable in aqueous solution even in the presence of a strong magnetic field. Out of various IONPs sizes, highest specific absorption rate (SAR) value of 5020 W g-1 was obtained with 45 nm GO-IONPs nanocomposites at a frequency and alternating magnetic field of 400 kHz and 32.5 kA m-1, respectively. The calculated intrinsic loss power (ILP) was 12.21 nH m2 kg-1, which is one of the highest ILP values reported for synthesized IONPs to the best of our knowledge. To enhance the excellent colloidal stability in biological environment, the GO-IONPs nanocomposites can be further grafted with polyethylene glycol (PEG) because agglomeration of pristine GO sheets occurs because of adsorption of cations. High ILP values could be well maintained even after PEG coating. The PEGylated 45 nm GO-IONP showed excellent antitumor efficacy in 4T1-tumor model mice by inhibiting tumor progression within a safe dosage range. Overall, the novel nanocomposite in this work-PEG-GO-IONP-possesses high hyperthermia performance, excellent colloidal stability in biological environment, and availability of functional groups in GO and can be utilized for tagging in various biomedical applications.

Metallization of 3D Printed Polymers and Their Application as a Fully Functional Water-Splitting System.

In this work, the plating of high-quality amorphous nickel-phosphorous coating with low resistivity of 0.45 µΩ m (298 K) on complex 3D printed polymeric structures with high uniformity is reported. Such a polymer metallization results in an effective conductivity of 4.7 × 104 S m-1. This process also allows flexible structures to maintain their flexibility along with the conductivity. Octet-truss structures with nickel-iron-(oxo) hydroxide nanosheets electrodeposited onto further displays excellent water-splitting performance as catalytic electrodes, i.e., in KOH (1 m, aq), a low oxygen evolution reaction (OER) overpotential of 197 mV at 10 mA cm-2 and Tafel slope of 51 mV dec-1. Using this light-weight electrode with high specific area, strength, and corrosion resistance properties, a fully functional water-splitting system is designed and fabricated through the concentric integration of 3D printed components. A dense polymeric mesh implemented is also demonstrated as an effective separator of hydrogen and oxygen bubbles in this system.

Ceramic Robocasting: Recent Achievements, Potential, and Future Developments.

Additive manufacturing (AM) of ceramic materials has attracted tremendous attention in recent years, due to its potential to fabricate suitable advanced ceramic structures for various engineering applications. Robocasting, a subset of ceramic AM, is an ideal technique for constructing fine and dense ceramic structures with geometrically complex morphology. With the freedom and convenience to deposit various materials within any 3D spatial position, ceramic robocasting opens up unlimited opportunities, which are otherwise hardly attainable from other AM techniques. Here, a summary of the recent progress on the fabrication of single and multi-ceramic structures by robocasting is provided, as well as the prospects of achieving shapeable ceramic structures. The current challenges in ceramic robocasting and an outlook on its development, especially toward the fabrication of self-shaping ceramic structures, are also discussed.

Hierarchical Design of NiOOH@Amorphous Ni-P Bilayer on a 3D Mesh Substrate for High-Efficiency Oxygen Evolution Reaction.

Recently, 3d metal phosphide and metal-phosphorus alloy have been intensively studied for the oxygen evolution reaction (OER). Research work has indicated that the presence of phosphorus could lead to the formation of a phosphide/(hydro)-oxide core/shell structure. In this work, we have developed a fabrication technique for a robust NiOOH@amorphous Ni-P bilayer on a zirconia mesh support through the collaboration of electroless deposition and robocasting. During the electroless deposition, a fully amorphous structure can be obtained with a certain phosphorus content (7-8 wt %). Relatively thick films (in the order of 5 µm) had an excellent adhesion on the mesh structure because of the large curvature. A stable Ni oxy/hydroxide surface (∼200 nm) can be formed in bilayer nature (NiOOH/Ni-P) due to preactivation. The combination of catalyst active sites on the surface and high conductivity of metallic body enables good OER performance with an overpotential of 286 mV at a current density of 10 mA cm-2. Together with excellent chemical stability and mechanical strength of the ceramic substrate, this novel combination gives rather excellent adhesion and stability in alkaline solution and provides a different angle for the hierarchical design of corrosion resistant and high-performance OER electrodes for industry.

Low-Field Dynamic Magnetic Separation by Self-Fabricated Magnetic Meshes for Efficient Heavy Metal Removal.

Wastewater contaminated with heavy metals is a worldwide concern due to the toxicity to human and animals. The current study presents an incorporation of adsorption and low-field dynamic magnetic separation technique for the treatment of heavy-metal-contaminated water. The key components are the eco-fabricated magnetic filter with mesh architectures (constituted of a soft magnetic material (Ni,Zn)Fe2O4) and poly(acrylic acid) (PAA)-coated quasi-superparamagnetic Fe3O4 nanoparticles (NPs). PAA-coated Fe3O4 NPs possess high adsorption capacity of heavy metal ions including Pb, Ni, Co, and Cu and can be easily regenerated after the adjustment of pH. Moreover, magnetic mesh filter has shown excellent collection ability of quasi-superparamagnetic particles under a magnetic field as low as 0.7 kOe (0.07 T) and can easily release these particles during ultrasonic washing when small magnets are removed. In the end, after one filtration process, the heavy metal concentration can be significantly decreased from 1.0 mg L-1 to below the drinking water standard recommended by the World Health Organization (e.g., less than 0.01 mg L-1 for Pb). Overall, a proof-of-concept adsorption and subsequent low-field dynamic separation technique is demonstrated as an economical and efficient route for heavy metal removal from wastewater.

Few-layer MoS2-anchored graphene aerogel paper for free-standing electrode materials.

To reduce the reliance on polymeric binders, conductive additives, and metallic current collectors during the electrode preparation process, as well as to assess the true performance of lithium ion battery (LIB) anodes, a free-standing electrode has to be meticulously designed. Graphene aerogel is a popular scaffolding material that has been widely used with embedded nanoparticles for application in LIB anodes. However, the current graphene aerogel/nanoparticle composite systems still involve decomposition into powder and the addition of additives during electrode preparation because of the thick aerogel structure. To further enhance the capacity of the system, MoS2 was anchored onto a graphene aerogel paper and the composite was used directly as an LIB anode. The resultant additive-free MoS2/graphene aerogel paper composite exhibited long cyclic performance with 101.1% retention after 700 cycles, which demonstrates the importance of free-standing electrodes in enhancing cyclic stability.

Synthesis of Ferromagnetic Fe0.6 Mn0.4 O Nanoflowers as a New Class of Magnetic Theranostic Platform for In Vivo T1 -T2 Dual-Mode Magnetic Resonance Imaging and Magnetic Hyperthermia Therapy.

Uniform wüstite Fe0.6 Mn0.4 O nanoflowers have been successfully developed as an innovative theranostic agent with T1 -T2 dual-mode magnetic resonance imaging (MRI), for diagnostic applications and therapeutic interventions via magnetic hyperthermia. Unlike their antiferromagnetic bulk counterpart, the obtained Fe0.6 Mn0.4 O nanoflowers show unique room-temperature ferromagnetic behavior, probably due to the presence of an exchange coupling effect. Combined with the flower-like morphology, ferromagnetic Fe0.6 Mn0.4 O nanoflowers are demonstrated to possess dual-modal MRI sensitivity, with longitudinal relaxivity r1 and transverse relaxivity r2 as high as 4.9 and 61.2 mm(-1) s(-1) [Fe]+[Mn], respectively. Further in vivo MRI carried out on the mouse orthotopic glioma model revealed gliomas are clearly delineated in both T1 - and T2 -weighted MR images, after administration of the Fe0.6 Mn0.4 O nanoflowers. In addition, the Fe0.6 Mn0.4 O nanoflowers also exhibit excellent magnetic induction heating effects. Both in vitro and in vivo magnetic hyperthermia experimentation has demonstrated that magnetic hyperthermia by using the innovative Fe0.6 Mn0.4 O nanoflowers can induce MCF-7 breast cancer cell apoptosis and a complete tumor regression without appreciable side effects. The results have demonstrated that the innovative Fe0.6 Mn0.4 O nanoflowers can be a new magnetic theranostic platform for in vivo T1 -T2 dual-mode MRI and magnetic thermotherapy, thereby achieving a one-stop diagnosis cum effective therapeutic modality in cancer management.

Nanostructured magnetic nanocomposites as MRI contrast agents.

Magnetic resonance imaging (MRI) has become an integral part of modern clinical imaging due to its non-invasiveness and versatility in providing tissue and organ images with high spatial resolution. With the current MRI advancement, MRI imaging probes with suitable biocompatibility, good colloidal stability, enhanced relaxometric properties and advanced functionalities are highly demanded. As such, MRI contrast agents (CAs) have been an extensive research and development area. In the recent years, different inorganic-based nanoprobes comprising inorganic magnetic nanoparticles (MNPs) with an organic functional coating have been engineered to obtain a suitable contrast enhancement effect. For biomedical applications, the organic functional coating is critical to improve colloidal stability and biocompatibility. Simultaneously, it also provides a building block for generating a higher dimensional secondary structure. In this review, the combinatorial design approach by a self-assembling pre-formed hydrophobic inorganic MNPs core (from non-polar thermolysis synthesis) into various functional organic coatings (e.g. ligands, amphiphilic polymers and graphene oxide) to form water soluble nanocomposites will be discussed. The resultant magnetic ensembles were classified based on their dimensionality, namely, 0-D, 1-D, 2-D and 3-D structures. This classification provides further insight into their subsequent potential use as MRI CAs. Special attention will be dedicated towards the correlation between the spatial distribution and the associated MRI applications, which include (i) coating optimization-induced MR relaxivity enhancement, (ii) aggregation-induced MR relaxivity enhancement, (iii) off-resonance saturation imaging (ORS), (iv) magnetically-induced off-resonance imaging (ORI), (v) dual-modalities MR imaging and (vi) multifunctional nanoprobes.

Tailoring a two-dimensional graphene oxide surface: dual T1 and T2 MRI contrast agent materials.

A generalized strategy for developing a hybrid two-dimensional nanostructured dual T1-T2 MRI contrast agent (CA), by co-loading graphene oxide with both Mn-doped Fe3O4 (T2 agent) and MnO (T1 agent) magnetic nanoparticles, is reported. Typical T1/T2 signal quenching, due to magnetic coupling, was not observed because of the fair T1 CA separation distance from the T2 CA on the graphene oxide. The resultant two-dimensional nanostructured MRI CA complements the existing dual T1-T2 MRI CA libraries.

Engineered water-soluble two-dimensional magnetic nanocomposites: towards highly magnetic relaxometric properties.

Water dispersible two-dimensional magnetic nanocomposites are formed by phase-transferring hydrophobic manganese-doped ferrite nanoparticles (MFPs) into aqueous solvent using a one-step simple approach involving only graphene oxide (GO) as the phase transfer agent. The resultant hydrophilic magnetic nanocomposites (MFNs) are surprisingly stable in the aqueous phase despite its large hydrodynamic size (dhyd). Because of its unique construct that promotes water accessibility towards the MFP core, large MFNs loaded with an 18 nm MFP core (MFN-18; dhyd = 577.9 nm) exhibits transverse relaxivity (r2) up to ∼6.8 times (r2 = 800.8 mM [Mn + Fe](-1) s(-1)) higher than the typical individually coated MFP-18 with amphiphilic brush copolymers (r2 = 117.3 mM [Mn + Fe](-1) s(-1)). Meanwhile, the overall nanocomposites dhyd can be further reduced by employing a smaller pre-sonicated GO sheet phase transfer agent. As a result of using small GO sheets with enhanced hydrophilicity, the r2 of small MFN-18* nanocomposites (dhyd = 224.9 nm) increases by approximately 37% (r2 = 1097.4 mM [Mn + Fe](-1) s(-1)) as compared to larger MFN-18. From a simple comparative study among various magnetic nanocomposites involving a MFP-18 core, the high MFN-18 r2 relaxivity value can be attributed to enhanced water diffusion and exchange due to the GO sheet, allowing better interaction between magnetic the MFP core and water protons. The proposed method can be readily extended to convert other types of hydrophobic nanoparticles into water-dispersible nanocomposites.

Graphene oxide based fluorescent nanocomposites for cellular imaging.

Carbon based 2-D material graphene oxide (GO) is a promising platform for preparing composites for biomedical applications because of its superior water solubility and low toxicity. Herein, we reported a convenient route to prepare fluorescent nanocomposites incorporating water-soluble GO sheets and Zn doped AgInS2 nanoparticles. According to the study, the photoluminescence of the Zn doped AgInS2 nanoparticles was well maintained after the hybridization using GO. No obvious emission shift was observed and the PL intensity was stable for over three months with negligible quenching. The PEGylated AIZS-GO nanocomposites could be readily up-taken by NIH/3T3 cells (mouse embryonic fibroblast cell line) while no distinct cytotoxicity was observed. The subsequent in vitro cellular imaging of NIH/3T3 cells proved that the as-prepared AIZS-GO-PEG nanocomposites were potential fluorescent probes for biomedical targeting and imaging.

Multifunctional PEGylated nanoclusters for biomedical applications.

A simple and versatile synthesis method to form water soluble multifunctional nanoclusters using polyethylene glycol (PEG) functionalized poly(maleic anhydride-alt-1-octadecene) amphiphilic brush copolymers (PMAO-g-PEG) was presented. Simply by tuning the core size and the initial nanocrystal concentration, manganese ferrite nanoparticles (MFNPs) were used to demonstrate the versatility of tuning the loading amount of the nanoclusters. The resultant nanoclusters were found to have a well-controlled spherical shape. When Zn-doped AgInS2 quantum dots (AIZS QDs) were loaded together with the MFNP nanocrystals, bi-functional nanoclusters with fluorescent and magnetic behaviors were obtained. Such bi-functional nanoclusters were also successfully demonstrated for cellular bio-imaging. Moreover, the presence of another type of nanocrystals together with MFNPs was found to have a negligible effect on the overall properties of the nanoclusters as demonstrated by the MR relaxivity test. From the time-dependent colloidal stability test, it was found that the presence of the PEG chain grafted onto PMAO was able to reduce protein adsorption onto the nanocluster surface. An in vitro study on NIH/3T3 demonstrated the biocompatibility of the nanoclusters. Such biocompatible and colloidally stable nanoclusters with an approximate size of 80-120 nm were suitable for both MRI and cell labeling applications.