Iron oxide-based nanomagnets in nanomedicine: fabrication and applications

Iron oxide-based nanomagnets have attracted a great deal of attention in nanomedicine over the past decade. Down to the nanoscale, superparamagnetic iron oxide nanoparticles can only be magnetized in the presence of an external magnetic field, which makes them capable of forming stable colloids in a physio-biological medium. Their superparamagnetic property, together with other intrinsic properties, such as low cytotoxicity, colloidal stability, and bioactive molecule conjugation capability, makes such nanomagnets ideal in both in-vitro and in-vivo biomedical applications. In this review, a chemical, physical, and biological synthetic approach to prepare iron oxide-based nanomagnets with different physicochemical properties was illustrated and compared. The growing interest in iron oxide-based nanomagnets with multifunctionalities was explored in cancer diagnostics and treatment, focusing on their combined roles in a magnetic resonance contrast agent, hyperthermia, and magnetic force assisted drug delivery. Iron oxides as magnetic carriers in gene therapy were reviewed with a focus on the sophisticated design and construction of magnetic vectors. Finally, the iron oxide-based nanomagnet also represents a very promising tool in particle/cell interfacing in controlling cellular functionalities, such as adhesion, proliferation, differentiation, and cell patterning, in stem cell therapy and tissue engineering applications

High-Throughput Top-Down Fabrication of Uniform Magnetic Particles

Ion Beam Aperture Array Lithography was applied to top-down fabrication of large dense (108–109 particles/cm2) arrays of uniform micron-scale particles at rates hundreds of times faster than electron beam lithography. In this process, a large array of helium ion beamlets is formed when a stencil mask containing an array of circular openings is illuminated by a broad beam of energetic (5–8 keV) ions, and is used to write arrays of specific repetitive patterns. A commercial 5-micrometer metal mesh was used as a stencil mask; the mesh size was adjusted by shrinking the stencil openings using conformal sputter-deposition of copper. Thermal evaporation from multiple sources was utilized to form magnetic particles of varied size and thickness, including alternating layers of gold and permalloy. Evaporation of permalloy layers in the presence of a magnetic field allowed creation of particles with uniform magnetic properties and pre-determined magnetization direction. The magnetic properties of the resulting particles were characterized by Vibrating Sample Magnetometry. Since the orientation of the particles on the substrate before release into suspension is known, the orientation-dependent magnetic properties of the particles could be determined

Mapping the Complex Morphology of Cell Interactions with Nanowire Substrates Using FIB-SEM

Using high resolution focused ion beam scanning electron microscopy (FIB-SEM) we study the details of cell-nanostructure interactions using serial block face imaging. 3T3 Fibroblast cellular monolayers are cultured on flat glass as a control surface and on two types of nanostructured scaffold substrates made from silicon black (Nanograss) with low- and high nanowire density. After culturing for 72 hours the cells were fixed, heavy metal stained, embedded in resin, and processed with FIB-SEM block face imaging without removing the substrate. The sample preparation procedure, image acquisition and image post-processing were specifically optimised for cellular monolayers cultured on nanostructured substrates. Cells display a wide range of interactions with the nanostructures depending on the surface morphology, but also greatly varying from one cell to another on the same substrate, illustrating a wide phenotypic variability. Depending on the substrate and cell, we observe that cells could for instance: break the nanowires and engulf them, flatten the nanowires or simply reside on top of them. Given the complexity of interactions, we have categorised our observations and created an overview map. The results demonstrate that detailed nanoscale resolution images are required to begin understanding the wide variety of individual cells' interactions with a structured substrate. The map will provide a framework for light microscopy studies of such interactions indicating what modes of interactions must be considered

Recombinant human Hsp70 protects against lipoteichoic acid-induced inflammation manifestations at the cellular and organismal levels

It has been previously reported that pretreatment with exogenous heat shock protein 70 (Hsp70) is able to protect cells and animals from the deleterious effects of bacterial lipopolysaccharide (LPS) produced by Gram-negative bacteria. However, the effects of Hsp70 pretreatment on lipoteichoic acid (LTA) challenge resulted from Gram-positive bacteria infection have not been fully elucidated. In this study, we demonstrated that preconditioning with human recombinant Hsp70 ameliorates various manifestations of systematic inflammation, including reactive oxygen species, TNFα, and CD11b/CD18 adhesion receptor expression induction observed in different myeloid cells after LTA addition. Therefore, exogenous Hsp70 may provide a mechanism for controlling excessive inflammatory responses after macrophage activation. Furthermore, in a rat model of LTA-induced sepsis, we demonstrated that prophylactic administration of exogenous human Hsp70 significantly exacerbated numerous homeostatic and hemodynamic disturbances induced by LTA challenge and partially normalized the coagulation system and multiple biochemical blood parameters, including albumin and bilirubin concentrations, which were severely disturbed after LTA injections. Importantly, prophylactic intravenous injection of Hsp70 before LTA challenge significantly reduced mortality rates. Thus, exogenous mammalian Hsp70 may serve as a powerful cellular defense agent against the deleterious effects of bacterial pathogens, such as LTA and LPS. Taken together, our findings reveal novel functions of this protein and establish exogenous Hsp70 as a promising pharmacological agent for the prophylactic treatment of various types of sepsis