Magnetothermally Activated Nanometer-level Modular Functional Group Grafting of Nanoparticles.

Nanoparticles with multifunctionality and high colloidal stability are essential for biomedical applications. However, their use is often hindered by the formation of thick coating shells and/or nanoparticle agglomeration. Herein, we report a single nanoparticle coating strategy to form 1 nm polymeric shells with a variety of chemical functional groups and surface charges. Under exposure to alternating magnetic field, nanosecond thermal energy pulses trigger a polymerization in the region only a few nanometers from the magnetic nanoparticle (MNP) surface. Modular coatings containing functional groups, according to the respective choice of monomers, are possible. In addition, the surface charge can be tuned from negative through neutral to positive. We adopted a coating method for use in biomedical targeting studies where obtaining compact nanoparticles with the desired surface charge is critical. A single MNP with a zwitterionic charge can provide excellent colloidal stability and cell-specific targeting.

Preparation of drug-immobilized anti-adhesion agent using visible light-curable alginate derivative containing furfuryl group.

This study demonstrated the anti-adhesion and wound healing effect of a visible light curable anti-adhesion agent using an alginate derivative modified with a furfuryl moiety. Visible light-curable furfuryl alginate (F-Alg) was prepared in conjugation with alginate and furfurylamine by an amide coupling reaction, and the conjugated F-Alg was characterized by 1H NMR analysis. The cytotoxicity, cell adhesion, and cell permeability of the F-Alg were evaluated for use in anti-adhesion applications. Drug immobilization and protein release were assessed to verify whether the alginate derivatives and drugs were photo-immobilized. In in vivo anti-adhesion testing, the new anti-adhesion agent prepared in this study acted as a physical protective layer by forming a biofilm on the surgical site. Additionally, along with gradual decomposition of the photo-crosslinked alginate derivative, the immobilized drug was released, and additional effects such as accelerated wound healing are expected. Thus, visible light-curable F-Alg has good application potential as an anti-adhesion agent.

Biocompatible, drug-loaded anti-adhesion barrier using visible-light curable furfuryl gelatin derivative.

Recently, many of studies have been attempted to determine how to decrease adhesion. To effectively prevent adhesion, decrease in unnecessary surgical procedures, prevention of contact with other tissue, and drug treatment for inflammation are required. However, current anti-adhesion materials have disadvantages. To solve current problems, we prepared a biocompatible drug-loaded anti-adhesion barrier using a visible-light curable furfuryl gelatin derivative. We used riboflavin as a photo-initiator in the photo-curing process. The biocompatibility of riboflavin was estimated compared with that of Rose Bengal. In addition, the curing ratio was measured to determine whether riboflavin initiated photo-curing. We also evaluated the curing ratio of riboflavin according to the concentration of F-gelatin and the photo-irradiation time. A drug used to decrease inflammation that causes adhesion should not disappear from the surgical site and should also be released consistently. For this, we observed the release profiles of photo-immobilized ibuprofen with different concentrations of F-gelatin. Because an anti-adhesion barrier should protect from bacterial infection we evaluated the protective ability of a barrier formed by F-gelatin. In conclusion, a drug-loaded anti-adhesion barrier was prepared using a visible-light curable furfuryl gelatin derivative, with riboflavin as a photo-initiator. We expect that this drug-loaded anti-adhesion barrier effectively decrease adhesion formation.

Visible and UV-curable chitosan derivatives for immobilization of biomolecules.

Chitosan, which has many biocompatible properties, is used widely in medical field like wound healing, drug delivery and so on. Chitosan could be used as a biomaterial to immobilize protein-drug. There are many methods to immobilize protein-drug, but they have some drawbacks such as low efficiency and denaturation of protein. Therefore, photo-immobilization method is suggested to immobilize protein-drug. Photo-immobilization method is simple-reaction and also needs no additional crosslinking reagent. There has been some effort to modify chitosan to have an ability of photo-immobilization. Generally, visible and UV light reactive chitosan derivatives were prepared. Various types of photo-curable chitosan derivatives showed possibility for application to medical field. For example, they showed ability for protein-immobilization and some of them showed wound-healing effect, anti-adhesive effect, or property to interact directly with titanium surface. In this study, we introduce many types of photo-curable chitosan derivative and their possibility of medical application.

Ultrathin Interface Regime of Core-Shell Magnetic Nanoparticles for Effective Magnetism Tailoring.

The magnetic exchange coupling interaction between hard and soft magnetic phases has been important for tailoring nanoscale magnetism, but spin interactions at the core-shell interface have not been well studied. Here, we systematically investigated a new interface phenomenon termed enhanced spin canting (ESC), which is operative when the shell thickness becomes ultrathin, a few atomic layers, and exhibits a large enhancement of magnetic coercivity (HC). We found that ESC arises not from the typical hard-soft exchange coupling but rather from the large magnetic surface anisotropy (KS) of the ultrathin interface. Due to this large increase in magnetism, ultrathin core-shell nanoparticles overreach the theoretical limit of magnetic energy product ((BH)max) and exhibit one of the largest values of specific loss power (SLP), which testifies to their potential capability as an effective mediator of magnetic energy conversion.

Quantitative Measurements of Size-Dependent Magnetoelectric Coupling in Fe3O4 Nanoparticles.

Bulk magnetite (Fe3O4), the loadstone used in magnetic compasses, has been known to exhibit magnetoelectric (ME) properties below ∼10 K; however, corresponding ME effects in Fe3O4 nanoparticles have been enigmatic. We investigate quantitatively the ME coupling of spherical Fe3O4 nanoparticles with uniform diameters (d) from 3 to 15 nm embedded in an insulating host, using a sensitive ME susceptometer. The intrinsic ME susceptibility (MES) of the Fe3O4 nanoparticles is measured, exhibiting a maximum value of ∼0.6 ps/m at 5 K for d = 15 nm. We found that the MES is reduced with reduced d but remains finite until d = ∼5 nm, which is close to the critical thickness for observing the Verwey transition. Moreover, with reduced diameter the critical temperature below which the MES becomes conspicuous increased systematically from 9.8 K in the bulk to 19.7 K in the nanoparticles with d = 7 nm, reflecting the core-shell effect on the ME properties. These results point to a new pathway for investigating ME effect in various nanomaterials.

Size-controlled construction of magnetic nanoparticle clusters using DNA-binding zinc finger protein.

Nanoparticle clusters (NPCs) have attracted significant interest owing to their unique characteristics arising from their collective individual properties. Nonetheless, the construction of NPCs in a structurally well-defined and size-controllable manner remains a challenge. Here we demonstrate a strategy to construct size-controlled NPCs using the DNA-binding zinc finger (ZnF) protein. Biotinylated ZnF was conjugated to DNA templates with different lengths, followed by incubation with neutravidin-conjugated nanoparticles. The sequence specificity of ZnF and programmable DNA templates enabled a size-controlled construction of NPCs, resulting in a homogeneous size distribution. We demonstrated the utility of magnetic NPCs by showing a three-fold increase in the spin-spin relaxivity in MRI compared with Feridex. Furthermore, folate-conjugated magnetic NPCs exhibited a specific targeting ability for HeLa cells. The present approach can be applicable to other nanoparticles, finding wide applications in many areas such as disease diagnosis, imaging, and delivery of drugs and genes.

Magnetic nanoparticles for ultrafast mechanical control of inner ear hair cells.

We introduce cubic magnetic nanoparticles as an effective tool for precise and ultrafast control of mechanosensitive cells. The temporal resolution of our system is ∼1000 times faster than previously used magnetic switches and is comparable to the current state-of-the-art optogenetic tools. The use of a magnetism-gated switch reported here can address the key challenges of studying mechanotransduction in biological systems. The cube-shaped magnetic nanoparticles are designed to bind to components of cellular membranes and can be controlled with an electromagnet to exert pico-Newtons of mechanical force on the cells. The cubic nanoparticles can thus be used for noncontact mechanical control of the position of the stereocilia of an inner ear hair cell, yielding displacements of tens of nanometers, with sub-millisecond temporal resolution. We also prove that such mechanical stimulus leads to the influx of ions into the hair cell. Our study demonstrates that a magnetic switch can yield ultrafast temporal resolution, and has capabilities for remote manipulation and biological specificity, and that such magnetic system can be used for the study of mechanotransduction processes of a wide range of sensory systems.

Magnetically triggered dual functional nanoparticles for resistance-free apoptotic hyperthermia.

Overcoming resistance: Heat-treated cancer cells possess a protective mechanism for resistance and survival. Resistance-free apoptosis-inducing magnetic nanoparticles (RAINs) successfully promote hyperthermic apoptosis, obstructing cell survival by triggering two functional units of heat generation and the release of geldanamycin (GM) for heat shock protein (Hsp) inhibition under an alternating magnetic field (AMF).

Correlation of expression and activity of matrix metalloproteinase-9 and -2 in human gingival cells of periodontitis patients.

PURPOSE: Matrix metalloproteinases (MMPs) are capable of degrading extracellular matrix, and they are inducible enzymes depending on an inflammatory environment such as periodontitis and bacterial infection in periodontal tissue. Gingival inflammation has been postulated to be correlated with the production of MMP-2 and MMP-9. The objective of this study was to quantify the expression and activity of MMP-9 and -2, and to determine the correlation between activity and expression of these MMPs in human gingival tissues with periodontitis. METHODS: The gingival tissues of 13 patients were homogenized in 500 µL of phosphate buffered saline with a protease inhibitor cocktail. The expression and activity of MMP-2 and -9 were measured by enzyme-linked immunosorbent assay and Western blot analysis, and quantified by a densitometer. For the correlation line, statistical analysis was performed using the Systat software package. RESULTS: MMP-9 was highly expressed in all gingival tissue samples, whereas MMP-2 was underexpressed compared with MMP-9. MMP-9 activity increased together with the MMP-9 expression level, with a positive correlation (r=0.793, P=0.01). The correlation was not observed in MMP-2. CONCLUSIONS: The expression of MMP-2 and -9 might contribute to periodontal physiological and pathological processes, and the degree of MMP-9 expression and activity are predictive indicators relevant to the progression of periodontitis.

Nanoscale magnetism control via surface and exchange anisotropy for optimized ferrimagnetic hysteresis.

With the aim of controlling nanoscale magnetism, we demonstrate an approach encompassing concepts of surface and exchange anisotropy while reflecting size, shape, and structural hybridization of nanoparticles. We visualize that cube has higher magnetization value than sphere with highest coercivity at 60 nm. Its hybridization into core-shell (CS) structure brings about a 14-fold increase in the coercivity with an exceptional energy conversion of magnetic field into thermal energy of 10600 W/g, the largest reported to date. Such capability of the CS-cube is highly effective for drug resistant cancer cell treatment.

Exchange-coupled magnetic nanoparticles for efficient heat induction.

The conversion of electromagnetic energy into heat by nanoparticles has the potential to be a powerful, non-invasive technique for biotechnology applications such as drug release, disease treatment and remote control of single cell functions, but poor conversion efficiencies have hindered practical applications so far. In this Letter, we demonstrate a significant increase in the efficiency of magnetic thermal induction by nanoparticles. We take advantage of the exchange coupling between a magnetically hard core and magnetically soft shell to tune the magnetic properties of the nanoparticle and maximize the specific loss power, which is a gauge of the conversion efficiency. The optimized core-shell magnetic nanoparticles have specific loss power values that are an order of magnitude larger than conventional iron-oxide nanoparticles. We also perform an antitumour study in mice, and find that the therapeutic efficacy of these nanoparticles is superior to that of a common anticancer drug.