Fang Lan

Superparamagnetic iron oxide nanoparticles as MRI contrast agents for non-invasive stem cell labeling and tracking.

Stem cells hold great promise for the treatment of multiple human diseases and disorders. Tracking and monitoring of stem cells in vivo after transplantation can supply important information for determining the efficacy of stem cell therapy. Magnetic resonance imaging (MRI) combined with contrast agents is believed to be the most effective and safest non-invasive technique for stem cell tracking in living bodies. Commercial superparamagnetic iron oxide nanoparticles (SPIONs) in the aid of transfection agents (TAs) have been applied to labeling stem cells. However, owing to the potential toxicity of TAs, more attentions have been paid to develop novel SPIONs with specific surface coating or functional moieties which facilitate effective cell internalization in the absence of TAs. This review aims to summarize the recent progress in the design and preparation of SPIONs as cellular MRI probes, to discuss their applications and current problems facing in stem cell labeling and tracking, and to offer perspectives and solutions for the future development of SPIONs in this field.

Magnetic responsive hydroxyapatite composite scaffolds construction for bone defect reparation

Introduction In recent years, interest in magnetic biomimetic scaffolds for tissue engineering has increased considerably. A type of magnetic scaffold composed of magnetic nanoparticles (MNPs) and hydroxyapatite (HA) for bone repair has been developed by our research group. Aim and methods In this study, to investigate the influence of the MNP content (in the scaffolds) on the cell behaviors and the interactions between the magnetic scaffold and the exterior magnetic field, a series of MNP-HA magnetic scaffolds with different MNP contents (from 0.2% to 2%) were fabricated by immersing HA scaffold into MNP colloid. ROS 17/2.8 and MC3T3-E1 cells were cultured on the scaffolds in vitro, with and without an exterior magnetic field, respectively. The cell adhesion, proliferation and differentiation were evaluated via scanning electron microscopy; confocal laser scanning microscopy; and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), alkaline phosphatase, and bone gla protein activity tests. Results The results demonstrated the positive influence of the magnetic scaffolds on cell adhesion, proliferation, and differentiation. Further, a higher amount of MNPs on the magnetic scaffolds led to more significant stimulation. Conclusion The magnetic scaffold can respond to the exterior magnetic field and engender some synergistic effect to intensify the stimulating effect of a magnetic field to the proliferation and differentiation of cells.

Facile synthesis of monodisperse superparamagnetic Fe3O4/PMMA composite nanospheres with high magnetization.

Monodisperse superparamagnetic Fe(3)O(4)/polymethyl methacrylate (PMMA) composite nanospheres with high saturation magnetization were successfully prepared by a facile novel miniemulsion polymerization method. The ferrofluid, MMA monomer and surfactants were co-sonicated and emulsified to form stable miniemulsion for polymerization. The samples were characterized by DLS, TEM, FTIR, XRD, TGA and VSM. The diameter of the Fe(3)O(4)/PMMA composite nanospheres by DLS was close to 90 nm with corresponding polydispersity index (PDI) as small as 0.099, which indicated that the nanospheres have excellent homogeneity in aqueous medium. The TEM results implied that the Fe(3)O(4)/PMMA composite nanospheres had a perfect core-shell structure with about 3 nm thin PMMA shells, and the core was composed of many homogeneous and closely packed Fe(3)O(4) nanoparticles. VSM and TGA showed that the Fe(3)O(4)/PMMA composite nanospheres with at least 65% high magnetite content were superparamagnetic, and the saturation magnetization was as high as around 39 emu g(-1) (total mass), which was only decreased by 17% compared with the initial bare Fe(3)O(4) nanoparticles.

Synthesis of superparamagnetic Fe3O4/PMMA/SiO2 nanorattles with periodic mesoporous shell for lysozyme adsorption

A new kind of nanorattle, composed of a Fe(3)O(4)/polymethyl methacrylate (PMMA) composite nanospherical core and mesoporous SiO(2) shell, has been successfully synthesized with the combination of a modified stöber method and a dual-template strategy, followed by alcohol dialysis. The nanorattles showed high efficiency in protein adsorption and separation.

Superparamagnetic Fe3O4/PMMA composite nanospheres as a nanoplatform for multimodal protein separation

Fe3O4/PMMA composite nanospheres with diameters ranging from 10 to 90 nm and saturation magnetisation varying from 29 to 39 emu g−1 have been successfully synthesized via a facile mini-emulsion polymerisation. Through simple surface modification, the nanospheres could be effectively used for fast protein adsorption, His-tagged protein separation and low concentration protein enrichment. The maximum adsorbed amount of lysozyme was as high as 478 mg g−1 near its isoelectric point using the Fe3O4/PMMA composite nanospheres. After enrichment with the nanosphere removed surfactants, the S/N of cytochrome C (cyt C) at a concentration of 0.5 mg L−1 remarkably increased to 68. Additionally, the surface functionalized nanospheres showed highly selective separation of His-tagged glutathione S-transferase (GST) from cell lysate. The results indicate the Fe3O4/PMMA composite nanospheres could be used as a nanoplatform for multimodal protein separation.

Synergic effect of magnetic nanoparticles on the electrospun aligned superparamagnetic nanofibers as a potential tissue engineering scaffold

In this study, aligned nanofibers have been fabricated by magnetic electrospinning, through the incorporation of magnetic nanoparticles (MNPs) into poly(lactic-co-glycolide) (PLGA) nanofibers. We further optimized the magnetic electrospinning process by systematically investigating the influence of the MNP and its content on the alignment of nanofibers. The biological effect of the aligned magnetic-electrospun nanofibers has been investigated by culturing C2C12 myoblasts on different nanofibers. The results indicated that the cells migrated and extended along the fiber arrangement. Because of the synergic effect of the magnetic nanoparticles on the nanofibers, the cells adhesion and proliferation is much more enhanced in our aligned nanofibers than the traditional ones in this experiment. Therefore, the magnetic-electrospun nanofibers could be a good candidate for an aligned tissue engineering scaffold.

Hollow superparamagnetic PLGA/Fe 3O 4 composite microspheres for lysozyme adsorption

Uniform hollow superparamagnetic poly(lactic-co-glycolic acid) (PLGA)/Fe(3)O(4) composite microspheres composed of an inner cavity, PLGA inner shell and Fe(3)O(4) outer shell have been synthesized by a modified oil-in-water (O/W) emulsion-solvent evaporation method using Fe(3)O(4) nanoparticles as a particulate emulsifier. The obtained composite microspheres with an average diameter of 2.5 μm showed excellent monodispersity and stability in aqueous medium, strong magnetic responsiveness, high magnetite content (>68%), high saturation magnetization (58 emu g(-1)) and high efficiency in lysozyme adsorption.

Protein Corona of Magnetic Hydroxyapatite Scaffold Improves Cell Proliferation via Activation of Mitogen-Activated Protein Kinase Signaling Pathway

The beneficial effect of magnetic scaffolds on the improvement of cell proliferation has been well documented. Nevertheless, the underlying mechanisms about the magnetic scaffolds stimulating cell proliferation remain largely unknown. Once the scaffold enters into the biological fluids, a protein corona forms and directly influences the biological function of scaffold. This study aimed at investigating the formation of protein coronas on hydroxyapatite (HA) and magnetic hydroxyapatite (MHA) scaffolds in vitro and in vivo, and consequently its effect on regulating cell proliferation. The results demonstrated that magnetic nanoparticles (MNP)-infiltrated HA scaffolds altered the composition of protein coronas and ultimately contributed to increased concentration of proteins related to calcium ions, G-protein coupled receptors (GPCRs), and MAPK/ERK cascades as compared with pristine HA scaffolds. Noticeably, the enriched functional proteins on MHA samples could efficiently activate of the MAPK/ERK signaling pathway, resulting in promoting MC3T3-E1 cell proliferation, as evidenced by the higher expression levels of the key proteins in the MAPK/ERK signaling pathway, including mitogen-activated protein kinase kinases1/2 (MEK1/2) and extracellular signal regulated kinase 1/2 (ERK1/2). Artificial down-regulation of MEK expression can significantly down-regulate the MAPK/ERK signaling and consequently suppress the cell proliferation on MHA samples. These findings not only provide a critical insight into the molecular mechanism underlying cellular proliferation on magnetic scaffolds, but also have important implications in the design of magnetic scaffolds for bone tissue engineering.

Polyacrylic acid brushes grafted from P(St-AA)/Fe3O4 composite microspheres via ARGET-ATRP in aqueous solution for protein immobilization

Recently, the atom transfer radical polymerization (ATRP) of acrylic monomers in many reaction systems has been successfully accomplished. However, its application in aqueous solution is still a challenging task. In this work, polyacrylic acid (PAA) brushes with tunable length were directly grafted from P(St-AA)/Fe3O4 composite microspheres in aqueous solution via an improved method, activators regenerated by electron transfer atom transfer radical polymerization (ARGET-ATRP). This reaction was carried out in environment-friendly solvent. As well, this method overcame the sensitivity of the catalyst. Due to the strong coordination interaction of carboxyl groups, PAA brushes were employed for immobilizing gold nanoparticles, which were prepared via the in situ reduction of chloroauric acid. The PAA brushes modified magnetic composite microspheres decorating with gold nanoparticles were efficient for specific immobilization and separation of bovine serum albumin (BSA) from aqueous solution under the external magnetic field.

Double-sided coordination assembly: superparamagnetic composite microspheres with layer-by-layer structure for protein separation

Double-sided coordination assembly via a two-step ligand exchange reaction was introduced to synthesize superparamagnetic poly(styrene-co-acrylic acid)/Fe3O4/polyacrylic acid (P(St-AA)/Fe3O4/PAA) composite microspheres for the first time. In the two-step ligand exchange reaction, the coordination interaction of carboxyl groups with the iron replaced the hydrogen bonding between triethylene glycol (TEG) and the Fe3O4 nanoparticles, resulting in the attachment of the Fe3O4 nanoparticles onto the surface of P(St-AA) colloidal template and the coating of monomeric AA onto the surface of Fe3O4 nanoparticles. The obtained P(St-AA)/Fe3O4/PAA composite microspheres showed excellent uniformity, high saturation magnetization, stability and efficient protein separation capacity. The equilibrium adsorption capacity of P(St-AA)/Fe3O4/PAA microspheres for lysozyme was as high as 1800 mg g−1. Functionalized with nitrilotriacetate-Ni2+ (NTA-Ni2+), such composite microspheres could efficiently and selectively capture polyhistidine-tagged glutathione-S-transferase (His-tagged-GST) from cell lysate.