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The evaluation of the toxicity of magnetic nanoparticles (MNPs) has attracted much attention in recent years. The current study aimed to investigate the cytotoxic effects of Fe 3 O 4 , oleic acid-coated Fe 3 O 4 (OA-Fe 3 O 4 ), and carbon-coated Fe (C-Fe) nanoparticles on human hepatoma BEL-7402 cells and the mechanisms. WST-1 assay demonstrated that the cytotoxicity of three types of MNPs was in a dose-dependent manner. G1 (Fe 3 O 4 and OA-Fe 3 O 4 ) phase and G2 (C-Fe) phase cell arrests and apoptosis induced by MNPs were detected by flow cytometry analysis. The increase in apoptosis was accompanied with the Bax over-expression, mitochondrial membrane potential decrease, and the release of cytochrome C from mitochondria into cytosol. Moreover, apoptosis was further confirmed by morphological and biochemical hallmarks, such as swollen mitochondria with lysing cristae and caspase-3 activation. Our results revealed that certain concentrations of the three types of MNPs affect BEL-7402 cells viability via cell arrest and inducing apoptosis, and the MNPs-induced apoptosis is mediated through the mitochondrial-dependent pathway. The influence potency of MNPs observed in all experiments would be: C-Fe > Fe 3 O 4 > OA-Fe 3 O 4 .

1D magnetic nanomaterials with iron, with the special physical properties and biological behaviour, have been found to possess the great promising applications in many fields. In this review, the components, structure, physicochemical properties, biocompatibility and in vitro and in vivo biomedical functions of magnetic nanowires (MNWs), nanorods (MNRs) with iron are summarised, especially their anisotropy shape and magnetism result in their many applications in biodetections and medical treatment fields. The potential future functions of these 1D magnetic nanomaterials compared to magnetic nanoparticles also is discussed by highlighting the possibility of integration with other metal‐compositions or bio‐compositions and with existing biotechnology as well as by pointing out their specific properties. Current limitations in the property improvement and issues related with the outcome of the MNRs in the body are also summarised in order to address the remaining challenge for the extended biomedical functions of MNRs in the clinical application field.

Magnetite (Fe3O4) nanoparticles are widely used in multiple biomedical applications due to their magnetic properties depending on the size, shape and organization of the crystals. However, the crystal growth and morphology of Fe3O4 nanoparticles remain difficult to control without using organic solvent or a high temperature. Inspired by the natural biomineralization process, a 14-mer bi-functional copolypeptide, leveraging the affinity of binding Fe3O4 together with targeting ovarian cancer cell A2780, was used as a template in the biomimetic mineralization of magnetite. Alongside this, a ginger extract was applied as an antioxidant and a size-conditioning agent of Fe3O4 crystals. As a result of the cooperative effects of the peptide and the ginger extract, the size and dispersibility of Fe3O4 were controlled based on the interaction of the amino acid and the ginger extract. Our study also demonstrated that the obtained particles with superparamagnetism could selectively be taken up by A2780 cells. In summary, the Fe3O4-QY-G nanoparticles may have potential applications in targeting tumor therapy or angiography.

In the present study, the effects of bone morphogenetic protein-2 (BMP-2), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) on regulation of rat osteoblast (ROB) maturation in vitro were investigated. It was found that the proliferation, differentiation and mineralization of ROBs were all dose-dependently increased at particular times in the case of treatment with only one growth factor. To investigate the effects of combined treatment, ROBs were treated with either a single application of a relatively high dose of each growth factor, or binary/triple combined applications of relatively low doses of the growth factors. Osteogenic differentiation was significantly promoted in the triple combination treatment of BMP-2, VEGF and bFGF compared with the single or binary combination treatments. The optimal timing of the triple combination to enhance osteogenesis was also tested. When bFGF and VEGF were added in the early stage, and BMP-2 and VEGF were added in the late stage, osteogenic differentiation of ROBs could be enhanced more effectively. These results could be used to construct bone tissue engineering scaffolds that release growth factors sequentially.

Objective Chitosan (CS) and polycaprolactone (PCL) were added into a nerve scaffold of poly(L‐lactide acid) (PLLA)/polypyrrole (PPy)‐based fibre films to solve the unmatch with the nerve strength and the aseptic inflammation from PLLA. Methods Poly (L‐lactide acid)‐polycaprolactone (PLLA/PCL) fibre films coated with chitosan (CS) and polypyrrole (PPy) were prepared by electrospinning of aligned PLLA/PCL fibres, electrochemical deposition of PPy nanoparticles and in situ doping of CS in PPy. PC12 cells were electrically stimulated with 100 mV for 2 hours every day via CS/PPy‐PLLA/PCL fibre film to promote the neurite growth. Results The surface conductivity and tensile strength of CS/PPy‐PLLA/PCL fibre films were 1.03 s/m and 13 MPa, respectively. CS content in fibre films was about 7.5 mg/cm2, improving the pH value (reached to 5.1) of immersion solution of the fibre film at 16 days. Compared with PPy‐PLLA/PCL fibre film, more and longer axons were grown out from PC12 cells cultured on CS/PPy‐PLLA/PCL fibre film, indicating the positive effect of CS in fibre film on axon growth. The cell differentiation rate and neurite length on CS/PPy‐PLLA/PCL fibre film reached to 38% and 75 μm, respectively. These results suggest the promotion of electrical stimulation on neurite growth and alignment. Conclusions A synergistic mechanism about the promotion of CS, electrical stimulation and aligned fibres on PC12 cells differentiation, axon outgrowth was proposed. These results indicated the potential application of CS/PPy‐PLLA/PCL fibre film in the field of the nerve repair and regeneration.

Angiogenesis, a complex biologic process, is regulated by a large number of angiogenic factors, including vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2). Whether Bone morphogenetic proteins-2 (BMP-2), the osteoinductive factor, could significantly reinforce the effect of VEGF and FGF-2 on angiogenesis has not been studied in detail. To study the positive effects of multiple growth factors on angiogenesis, HUVECs were treated with BMP-2, VEGF, or FGF-2 singly and in binary and ternary combinations. This study further investigates the optimal timing of the ternary combination of BMP-2, VEGF and FGF-2 for angiogenesis in the chorioallantoic membrane (FGF-2 CAM). Results of single applications of BMP-2, VEGF, or FGF-2 suggested that HUVECs angiogenesis could be promoted in a dose-dependent manner and that the optimal concentration of BMP, VEGF and FGF-2 was 10, 50 and 1 ng/mL, respectively. These results indicated that the angiogenic activity of VEGF and FGF-2 was amplified by combining with BMP-2. The ternary combination of BMP-2, VEGF and FGF-2 exhibited a positive and synergistic effect on HUVECs angiogenesis, with the lower concentrations of each factor (1 ng/mL of BMP-2, 25 ng/mL of VEGF and 0.1 ng/mL of FGF-2) being sufficient to show synergistic promotion. When VEGF and FGF-2 were added in the initial activation stage and BMP-2 was added in the maturation stage, both HUVECs angiogenesis in vitro and CAM angiogenesis in vivo could be enhanced more effectively. These results could provide a basis for the controlled release systems capable of delivering multiple factors sequentially to promote angiogenesis in tissue engineering.

Fe3O4 magnetic nanoparticles (Fe3O4-MNPs) have attracted much interest for their potential medical applications due to their desirable magnetic properties. However, their potential cytotoxicity, high RES clearance in circulation, and nonspecific distribution in tissue might be the main obstacles in practice. In the present study, a novel bi-functional 14-mer peptide with both ovarian carcinoma cells targeting and magnetic Fe3O4 nanoparticles affinity was designed and synthesized, and then a facile and effective modification method was developed to bestow the Fe3O4-MNPs with tumor-targeting capability via modification, using the bi-functional peptides. First, on the basis of a tumor-targeting 7-mer peptide QQTNWSL (Q-L) and another Fe3O4-MNPs-targeting 7-mer peptide TVNFKLY (T-Y)—screened by phage-displayed peptide libraries—two bi-functional 14-mer peptides sequenced as LSWNTQQ-YLKFNVT (abbreviated as LQ-YT) and QQTNWSL-YLKFNVT (QL-YT) were synthesized through combining the Q-L peptide and T-Y peptide in predetermined configurations. Their specificity for bonding with A2780 tumor cells and affinity for Fe3O4-MNPs were verified. Then the bi-functional 14-mer peptides were applied to modify the Fe3O4-MNPs. Results showed that both bi-functional 14-mer peptides could be conjugated to the Fe3O4-MNPs surface with high affinity. Immunofluorescence and Prussian blue staining assays indicated that the LQ-YT-modified Fe3O4-MNPs could specifically bond to A2780 tumor cells. In addition to our findings suggesting that more β-turns and random coils are conducive to increasing polypeptide surface area for binding and exposing the target group and bonding sites on LQ-YT to external targets, we demonstrated that the bi-functional 14-mer peptide has affinity for Fe3O4-MNPs, and that Fe3O4-MNPs, which was modified with a 14-mer peptide, could be bestowed with a targeting affinity for ovarian carcinoma cells.

Desirable scaffolds for tissue engineering should be biodegradable carriers to supply suitable microenvironments mimicked the extracellular matrices for desired cellular interactions and to provide supports for the formation of new tissues. In this work, a kind of slightly soluble bioactive ceramic akermanite (AKT) powders were aboratively selected and introduced in the PLGA matrix, a novel l-lactide modified AKT/poly (lactic-co-glycolic acid) (m-AKT/PLGA) composite scaffold was fabricated via a solvent casting-particulate leaching method improved by solvent self-proliferating process. The effects of m-AKT contents on properties of composite scaffolds and on MC3T3-E1 cellular behaviors in vitro have been primarily investigated. The fabricated scaffolds exhibited three-dimensional porous networks, in which homogenously distributed cavities in size of 300–400 μm were interconnected by some smaller holes in a size of 100–200 μm. Meanwhile, the mechanical structure of scaffolds was reinforced by the introduction of m-AKT. Moreover, alkaline ionic products released by m-AKT could neutralize the acidic degradation products of PLGA, and the apatite-mineralization ability of scaffolds could be largely improved. More valuably, significant promotions on adhesion, proliferation, and differentiation of MC3T3-E1 have been observed, which implied the calcium, magnesium and especially silidous ions released sustainably from composite scaffolds could regulate the behaviors of osteogenesis-related cells.

Macroporous magnetic Fe3O4 microparticles, which might act as both drug carriers and magnetocaloric media, were expected to have broad application prospects on magnetocaloric-responsively controlled drug release systems. A kind of macroporous magnetic Fe3O4 microparticle was prepared by an organic matter assisted open-cell hollow sphere (hollow sphere with holes on shell) assembly method in this study. 1-vinyl-2-pyrrolidinone (NVP) and 2-acrylamido-2-methyl propane sulfonic acid (AMPS) were selected as the template and the binder, respectively. Ferrous ions were specifically bound to carbonyl groups on NVP and were then reduced by NaBH4. The reduced irons underwent heterogeneous nucleation and grain growth to form Fe0/Fe3O4 microspheres consisting of a lot of nano-Fe0 grains, and were then assembled into Fe0/Fe3O4 microparticles wrapped by AMPS. Results indicate that NVP binding with ferrous ions can promote a self-polymerization process and the formation of Fe0/Fe3O4 microspheres, while AMPS enwrapping around the resultant microspheres can facilitate their assembly into larger aggregates. As a result, macroporous Fe3O4 microparticles composed of several open-cell hollow Fe3O4 microspheres can be obtained under a Kirkendall-controlled oxidation. Moreover, these as-prepared macroporous Fe3O4 microparticles possess a narrow particle size distribution and exhibit ferromagnetism (Ms = 66.14 emu/g, Mr = 6.33 emu/g, and Hc = 105.32 Oe). Our work, described here, would open up a novel synthesis method to assemble macroporous magnetic Fe3O4 microparticles for potential application in magnetocaloric-responsively controlled drug release systems.

Fe₃O₄ magnetic nanoparticles (Fe₃O₄-MNPs) have attracted much interest for their potential medical applications due to their desirable magnetic properties. However, their potential cytotoxicity, high RES clearance in circulation, and nonspecific distribution in tissue might be the main obstacles in practice. In the present study, a novel bi-functional 14-mer peptide with both ovarian carcinoma cells targeting and magnetic Fe₃O₄ nanoparticles affinity was designed and synthesized, and then a facile and effective modification method was developed to bestow the Fe₃O₄-MNPs with tumor-targeting capability via modification, using the bi-functional peptides. First, on the basis of a tumor-targeting 7-mer peptide QQTNWSL (Q-L) and another Fe₃O₄-MNPs-targeting 7-mer peptide TVNFKLY (T-Y)-screened by phage-displayed peptide libraries-two bi-functional 14-mer peptides sequenced as LSWNTQQ-YLKFNVT (abbreviated as LQ-YT) and QQTNWSL-YLKFNVT (QL-YT) were synthesized through combining the Q-L peptide and T-Y peptide in predetermined configurations. Their specificity for bonding with A2780 tumor cells and affinity for Fe₃O₄-MNPs were verified. Then the bi-functional 14-mer peptides were applied to modify the Fe₃O₄-MNPs. Results showed that both bi-functional 14-mer peptides could be conjugated to the Fe₃O₄-MNPs surface with high affinity. Immunofluorescence and Prussian blue staining assays indicated that the LQ-YT-modified Fe₃O₄-MNPs could specifically bond to A2780 tumor cells. In addition to our findings suggesting that more β-turns and random coils are conducive to increasing polypeptide surface area for binding and exposing the target group and bonding sites on LQ-YT to external targets, we demonstrated that the bi-functional 14-mer peptide has affinity for Fe₃O₄-MNPs, and that Fe₃O₄-MNPs, which was modified with a 14-mer peptide, could be bestowed with a targeting affinity for ovarian carcinoma cells.