Optical Imaging and High-Accuracy Quantification of Intracellular Iron Contents.

Precise quantification of intracellular iron contents is important to biomedical applications of magnetic nanoparticles. Current approaches for iron quantification rely on specialized instruments while most only yield iron quantities averaged over plenty of cells. Here, a simple and robust approach, combining digital optical microscopy with the Beer-Lambert's law, that allows for imaging stainable iron distribution in individual cells and the quantification of stainable iron contents with an unprecedented accuracy of femtogram per pixel, is presented. It is further shown that this approach enables studying of the internalization and reduction dynamics of super-paramagnetic iron oxide nanoparticles (SPIONs) by stem cells in single cell level.

Moderate cooling coprecipitation for extremely small iron oxide as a pH dependent T1-MRI contrast agent.

Iron based nanomedicine (IBNM) has been one powerful diagnostic tool as a magnetic resonance imaging (MRI) contrast agent (CA) in the clinic for years. Conventional IBNMs are generally employed as T2-MRI CAs, but most of them are constrained in clinical indication expansion by magnetic susceptibility artifacts. In comparison, extremely small iron oxide (ESIO) with a core size less than 5 nm has demonstrated the T1-MRI effect, which provides prospects for a Gd-based agent alternative. Nevertheless, currently developed ESIOs for T1-MRI CAs always require harsh conditions such as a high temperature and high boiling point reagent. Moreover, very few of the currently developed ESIOs meet the stringent pharmaceutical standard. Herein, on the basis of a crystal nuclear precipitation-dissolution equilibrium mechanism and outer/inner sphere T1-MRI theory, monodisperse ESIOs with an average size of 3.43 nm (polydispersity index of 0.104) are fabricated using a moderate cooling procedure with mild coprecipitation reaction conditions. The as-synthesized ESIOs display around 3-fold higher T1 MRI signal intensity than that of commercial Ferumoxytol (FMT), comparable to that of Gd-based CAs in vitro. Additionally, the T1-MRI performance of the ESIOs is pH dependent and delivers bright signal augmentation. Eventually, the internalization into mesenchymal stem cells of the ESIO is realized in the absence of a transferring agent. Considering the identical structure and composition of the ESIOs as compared to that of FMT, they could meet the pharmaceutical criteria, thus providing great potential as T1-MRI Cas, for instance as stem cell tracers.

Entry-Prohibited Effect of kHz Pulsed Magnetic Field Upon Interaction Between SPIO Nanoparticles and Mesenchymal Stem Cells.

OBJECTIVE: The interaction between superparamagnetic iron oxide (SPIO) nanoparticles and mesenchymal stem cells (MSCs) in the presence of pulsed magnetic field (PMF) has become an important area of research in recent years. METHODS: A parameter-adjustable pulsed magnetic field was developed based on the principle of insulated gate bipolar translator transistor-controlled discharge of large capacitances. The internalizations of SPIO nanoparticles by MSCs were investigated under the treatment of PMF in both intermittent stimulation mode and continuous stimulation mode. RESULTS: The intensities and frequencies of pulsed magnetic field can be adjustable in the range of 1.9-4.6 mT and 3-5 kHz, respectively. This PMF was safe to the MSCs. However, the uptake of SPIO nanoparticles by MSCs was significantly prohibited under the treatment of kHz-ranged PMF while the 10 Hz PMF enhanced the cellular uptake of nanoparticles. This phenomenon was relative with the magnetic effect of the PMF with different frequency. CONCLUSION: The PMF can be used to effectively regulate the cellular uptake of SPIO nanoparticles and the mechanism lies in the magnetic effect. SIGNIFICANCE: The interaction between SPIO nanoparticles and the MSCs is a fundamental and important issue for nanomedicine and stem cell research. Our results demonstrate that the external magnetic field can be used to regulate their interaction. We believe that this safe, facile, and flexible method will greatly promote the development and clinical translation of regenerative medicine and nanomedicine.

Adaptive Materials Based on Iron Oxide Nanoparticles for Bone Regeneration.

The paper provides a brief overview of the use of iron oxide nanoparticles (IONPs) in the areas of bone regenerative medicine. Reconstruction of bone defects caused by trauma, non-union, and bone tumor excision, still faces many challenges despite the intense investigations and advancement in bone-tissue engineering and bone regeneration over the past decades. IONPs have promising prospects in this field due to their controlled responsive characteristics in specific external magnetic fields and have been of great interest during the last few years. This Minireview aims to summarize the relevant progress and describes the following five aspects: (i) The general introduction of IONPs, with a focus on the magnetic properties as the base of application; (ii) using IONPs as tools to study and control stem cells for better treatment efficacy in stem-cell-based bone defect repair; (iii) the use of IONPs and their complexes in the delivery of therapeutic agents, including chemical drug molecules, growth factors, and genetic materials, to promote osteogenesis-related cell function and differentiation, healthy bone tissue growth, and functional reconstruction; (iv) magneto-mechanical actuation in the regulation of cells distribution, mechano-transduction membrane receptors activation, and mechanosensitive signaling pathways regulation, and (v) fabrication, characteristics, and in vitro and in vivo osteogenic effects of magnetic composite bone scaffolds. Ongoing prospects are also discussed.