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.Keywords: cell proliferation; magnetic hydroxyapatite scaffold; magnetic nanoparticles; MAPK signaling pathway; protein corona; tissue engineering;

•Combined strategy of self-polymerization and assembly for synthesis of SSINs.•DOPA as both functional monomer and cross-linking agent self-polymerized.•Lyz-imprinted cavities on polymerized DOPA are used for protein capture.A combination strategy of moderate self-polymerization and assembly technique was proposed to fabricate superparamagnetic surface imprinted nanocomposites (SSINs) for efficient protein recognition. Homogeneous Fe3O4/Poly (methyl methacrylate) (PMMA)/Poly (dihydroxyphenylacetic acid) (PDOPA) SSINs were obtained via self-polymerization of DOPA on the surface of Fe3O4/PMMA nanospheres in the presence of lysozyme (Lyz) as a template. The Lyz-imprinted Fe3O4/PMMA/PDOPA SSINs possessed average diameters of 200 nm, high magnetic content, high saturation magnetization, as well as excellent specific recognition capacity toward Lyz template, exhibiting their great potential for biomacromolecular recognition.Superparamagnetic surface imprinted nanocomposites (Fe3O4/PMMA/PDOPA SSINs) prepared via self-polymerization and assembly technique in moderate conditions.Download high-res image (93KB)Download full-size image

In this study, we report a facile and versatile strategy for preparing a type of pH-responsive superparamagnetic hybrid coassemblies featuring a series of controls over the morphology and multi-functionalization simultaneously and efficiently. Via the entanglement interactions, the combine of fixed PEG-b-P4VP modified Fe3O4 NPs (D-Fe3O4@mPEG-b-P4VP) and different well-designed free PEG-b-P4VP, which are analogous to two amphiphiles, contributes these hybrid superstructures with multiple, well-defined morphologies and targeted fluorescent properties. In contrast to other studies, our work overcame several defects (e.g., interior NPs’ randomness, cumbersome assembly parameter adjustment and functionalization) of the conventional assembly of modified inorganic NPs and demonstrated that this coassembly strategy can be used as a versatile tool for the controllable assembly of other NPs or polymers. Finally, taking the coassembly C1 as a desirable drug delivery carrier, good biocompatibility and pH-triggered drug release were successfully verified. The current study indicated that these magnetic coassemblies are promising as multifunctional and multipurpose carriers in biological, medical, catalytic, and coating applications.We present a facile and versatile strategy for preparation of a novel pH responsive superparamagnetic hybrid coassembly with a series of controllable morphologies and flexible desired properties simultaneously and efficiently.Download high-res image (105KB)Download full-size image

Glycoproteins are related to many biological activities and diseases and their effective capture and release from a complex mixture is of great significance in proteomics and diagnostics. However, to separate and target glycoproteins with high efficiency and selectivity is difficult, due to the interference of nanomaterials and other proteins in complicated samples. In this study, Fe3O4/carboxymethylated chitosan/poly(3-acrylaminophenylboronic acid) (Fe3O4/CMCS/PAAPBA) nanospheres with enhanced properties are prepared by a facile and economical method, and possess excellent morphology, uniform size (∼300 nm), high saturation magnetization (59 emu g−1), and high magnetic content (79%). Due to the introduction of PAAPBA, the Fe3O4/CMCS/PAAPBA nanospheres have been developed as a pH-responsive strategy to reversibly capture and release glycoproteins with high selectivity and recyclability in a pure protein, a model protein mixture and even a biological sample. Additionally, the Fe3O4/CMCS/PAAPBA nanospheres retained high separation efficiency (∼94%) in a pure protein system after being recycled five times, showing the great potential of the boronate functionalized, pH-stimuli-responsive, magnetic nanospheres in the biomedical field.

In recent years, it is becoming increasingly evident that once nanoparticles come into contact with biological fluids, a protein corona surely forms and critically affects the biological behaviors of nanoparticles. Herein, we investigate whether the formation of protein corona on the surface of superparamagnetic iron oxides (SPIOs) is influenced by static magnetic field. Under static magnetic field, there is no obvious variation in the total amount of protein adsorption, but the proportion of adsorbed proteins significantly changes. Noticeably, certain proteins including apolipoproteins, complement system proteins and acute phase proteins, increase in the protein corona of SPIOs in the magnetic field. More importantly, the magnetic-dependent protein corona of SPIOs enhances the cellular uptake of SPIOs into the normal cell line (3T3 cells) and tumor cell line (HepG2 cells), due to increased adsorption of apolipoprotein. In addition, SPIOs with the magnetic-dependent protein corona cause high cytotoxicity to 3T3 cells and HepG2 cells. This work discloses that superparamagnetism as a key feature of SPIOs affects the composition of protein corona to a large extent, which further alters the biological behaviors of SPIOs.

Solvent etching is a general method for the fabrication of hollow-structured nano/micro-spheres with multiple functions. In this study, we report a facile route for the preparation of hollow composite microspheres, which are amphiphilic and superparamagnetic. In a template of magnetic composite microspheres, P(St-AA)/Fe3O4/PAA, P(St-AA) was selectively etched, resulting in a hydrophobic hollow structure with a shell of hydrophilic polymeric brushes. The effects of etching on the morphology, hollow structure, saturation magnetization, amphiphilic property and cytocompatibility were investigated. Characterization showed that the hollow composite microspheres obtained possessed a well-defined spherical structure, a high saturation magnetization, amphiphilic properties and good cytocompatibility, making them promising as a potential biomaterial in magnetic resonance imaging and drug delivery systems.

A combination strategy of the inverse emulsion crosslinking approach and the colloidal assembly technique is first proposed to synthesize Fe3O4/histidine composite nanoclusters as new-type magnetic porous nanomaterials. The nanoclusters possess uniform morphology, high magnetic content and excellent protein adsorption capacity, exhibiting their great potential for bio-separation.

Tea polyphenol serves as an environmentally friendly ligand-exchange molecule to synthesize multifunctional metal-doped superparamagnetic iron oxide nanoparticles via a catechol–metal coordination interaction. The resultant particles not only exhibit excellent hydrophilicity and protein adsorption resistance, but also are applicable as magnetic resonance/fluorescent dual-imaging probes due to their high T2 relaxivity, autofluorescence and large cellular uptake.

•Magnetic composite microspheres were modified by PAA brushes via ARGET-ATRP.•ARGET-ATRP of the acrylic acid was directly carried out in aqueous solution.•PAA brushes were employed for immobilizing gold nanoparticles.•Magnetic microspheres with gold nanoparticles have specific recognition to BSA.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.

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.

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 cell's 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.

Surface functionalization of magnetic nanoparticles (MNPs) has been an exciting area of interest for researchers in biomedicine. In this paper, we introduce a new family of peptide dendritic ligands for functionalizing MNPs of superior quality. L-Lysine- and L-glutamic acid-based dendritic ligands with dopamine located at the focal points were fully designed and synthesized before the functionalization. Then ligands of different dendritic generations (G1 to G3) were immobilized on the surface of oleic-acid-coated hydrophobic MNPsvia ligand-exchange method to realize phase transfer. The two series of modified MNPs were systematically studied viaFTIR, TGA, XRD, TEM, DLS, VSM and zeta potential measurements. The modified MNPs exhibited an adjustable number of terminal functional groups and superior stability in aqueous solutions in a broad pH range. The surface existence of water-soluble polypeptide ligands promoted monodispersity of the particles and led to an increased hydrodynamic diameter under 30 nm from G1 to G3. After the ligand exchange process, the superparamagnetic behavior was successfully retained. The two series of modified MNPs exhibited approximate magnetization in the same generation, while the saturation magnetization of the MNPs decreased with increasing surface dendritic generation. MNPs functionalized with G1L-glutamic acid dendritic ligands had the highest saturation magnetization (55 emu g−1), which was larger than for the initial MNPs. This novel functionalization strategy provides a potential platform for designing and preparing highly stable ultrafine MNPs with high magnetization for biomedicinal applications.

Surface functionalization of magnetic nanoparticles (MNPs) has been an exciting area of interest for researchers in biomedicine. In this paper, we introduce a new family of peptide dendritic ligands for functionalizing MNPs of superior quality. L-Lysine- and L-glutamic acid-based dendritic ligands with dopamine located at the focal points were fully designed and synthesized before the functionalization. Then ligands of different dendritic generations (G1 to G3) were immobilized on the surface of oleic-acid-coated hydrophobic MNPsvia ligand-exchange method to realize phase transfer. The two series of modified MNPs were systematically studied viaFTIR, TGA, XRD, TEM, DLS, VSM and zeta potential measurements. The modified MNPs exhibited an adjustable number of terminal functional groups and superior stability in aqueous solutions in a broad pH range. The surface existence of water-soluble polypeptide ligands promoted monodispersity of the particles and led to an increased hydrodynamic diameter under 30 nm from G1 to G3. After the ligand exchange process, the superparamagnetic behavior was successfully retained. The two series of modified MNPs exhibited approximate magnetization in the same generation, while the saturation magnetization of the MNPs decreased with increasing surface dendritic generation. MNPs functionalized with G1L-glutamic acid dendritic ligands had the highest saturation magnetization (55 emu g−1), which was larger than for the initial MNPs. This novel functionalization strategy provides a potential platform for designing and preparing highly stable ultrafine MNPs with high magnetization for biomedicinal applications.

Glycoproteins are related to many biological activities and diseases and their effective capture and release from a complex mixture is of great significance in proteomics and diagnostics. However, to separate and target glycoproteins with high efficiency and selectivity is difficult, due to the interference of nanomaterials and other proteins in complicated samples. In this study, Fe3O4/carboxymethylated chitosan/poly(3-acrylaminophenylboronic acid) (Fe3O4/CMCS/PAAPBA) nanospheres with enhanced properties are prepared by a facile and economical method, and possess excellent morphology, uniform size (∼300 nm), high saturation magnetization (59 emu g−1), and high magnetic content (79%). Due to the introduction of PAAPBA, the Fe3O4/CMCS/PAAPBA nanospheres have been developed as a pH-responsive strategy to reversibly capture and release glycoproteins with high selectivity and recyclability in a pure protein, a model protein mixture and even a biological sample. Additionally, the Fe3O4/CMCS/PAAPBA nanospheres retained high separation efficiency (∼94%) in a pure protein system after being recycled five times, showing the great potential of the boronate functionalized, pH-stimuli-responsive, magnetic nanospheres in the biomedical field.