Sciatic nerve regeneration after traumatic injury using magnetic targeted adipose-derived mesenchymal stem cells.

Traumatic peripheral nerve injuries constitute a huge concern to public health. Nerve damage leads to a decrease or even loss of mobility of the innervated area. Adult stem cell therapies have shown some encouraging results and have been identified as promising treatment candidates for nerve regeneration. A major obstacle to that approach is securing a sufficient number of cells at the injured site to produce measurable therapeutic effects. The present work tackles this issue and demonstrates enhanced nerve regeneration ability promoted by magnetic targeted cell therapy in an in vivo Wallerian degeneration model. To this end, adipose-derived mesenchymal stem cells (AdMSC) were loaded with citric acid coated superparamagnetic iron oxide nanoparticles (SPIONs), systemically transplanted and magnetically recruited to the injured sciatic nerve. AdMSC arrival to the injured nerve was significantly increased using magnetic targeting and their beneficial effects surpassed the regenerative properties of the stand-alone cell therapy. AdMSC-SPIONs group showed a partially conserved nerve structure with many intact myelinated axons. Also, a very remarkable restoration in myelin basic protein organization, indicative of remyelination, was observed. This resulted in an improvement in nerve conduction, demonstrating functional recovery. In summary, our results demonstrate that magnetically assisted delivery of AdMSC, using a non-invasive and non-traumatic method, is a highly promising strategy to promote cell recruitment and sciatic nerve regeneration after traumatic injury. Last but not least, our results validate magnetic targeting in vivo exceeding previous reports in less complex models through cell magnetic targeting in vitro and ex vivo. STATEMENT OF SIGNIFICANCE: Traumatic peripheral nerve injuries constitute a huge public health concern. They can lead to a decrease or even loss of mobility of innervated areas. Due to their complex pathophysiology, current pharmacological and surgical approaches are only partially effective. Cell-based therapies have emerged as a useful tool to achieve full tissue regeneration. However, a major bottleneck is securing enough cells at injured sites. Therefore, our proposal combining biological (adipose derived mesenchymal stem cells) and nanotechnological strategies (magnetic targeting) is of great relevance, reporting the first in vivo experiments involving "magnetic stem cell" targeting for peripheral nerve regeneration. Using a non-invasive and non-traumatic method, cell recruitment in the injured nerve was improved, fostering nerve remyelination and functional recovery.

Kinetically Stable Nonequilibrium Gold-Cobalt Alloy Nanoparticles with Magnetic and Plasmonic Properties Obtained by Laser Ablation in Liquid.

Nonequilibrium nanoalloys are metastable solids obtained at the nanoscale under nonequilibrium conditions that allow the study of kinetically frozen atoms and the discovery of new physical and chemical properties. However, the stabilization of metastable phases in the nanometric size regime is challenging and the synthetic route should be easy and sustainable, for the nonequilibrium nanoalloys to be practically available. Here we report on the one-step laser ablation synthesis in solution (LASiS) of nonequilibrium Au-Co alloy nanoparticles (NPs) and their characterization on ensembles and at the single nanoparticle level. The NPs are obtained as a polycrystalline solid solution stable in air and water, although surface cobalt atoms undergo oxidation to Co(II). Since gold is a renowned plasmonic material and metallic cobalt is ferromagnetic at room temperature, these properties are both found in the NPs. Besides, surface conjugation with thiolated molecules is possible and it was exploited to obtain colloidally stable solutions in water. Taking advantage of these features, an array of magnetic-plasmonic dots was obtained and used for surface-enhanced Raman scattering experiments. Overall, this study confirms that LASiS is an effective method for the formation of kinetically stable nonequilibrium nanoalloys and shows that Au-Co alloy NPs are appealing magnetically responsive plasmonic building blocks for several nanotechnological applications.

Effect of Nanoclustering and Dipolar Interactions in Heat Generation for Magnetic Hyperthermia.

Biomedical magnetic colloids commonly used in magnetic hyperthermia experiments often display a bidisperse structure, i.e., are composed of stable nanoclusters coexisting with well-dispersed nanoparticles. However, the influence of nanoclusters in the optimization of colloids for heat dissipation is usually excluded. In this work, bidisperse colloids are used to analyze the effect of nanoclustering and long-range magnetic dipolar interaction on the magnetic hyperthermia efficiency. Two kinds of colloids, composed of magnetite cores with mean sizes of around 10 and 18 nm, coated with oleic acid and dispersed in hexane, and coated with meso-2,3-dimercaptosuccinic acid and dispersed in water, were analyzed. Small-angle X-ray scattering was applied to thoroughly characterize nanoparticle structuring. We proved that the magnetic hyperthermia performances of nanoclusters and single nanoparticles are distinctive. Nanoclustering acts to reduce the specific heating efficiency whereas a peak against concentration appears for the well-dispersed component. Our experiments show that the heating efficiency of a magnetic colloid can increase or decrease when dipolar interactions increase and that the colloid concentration, i.e., dipolar interaction, can be used to improve magnetic hyperthermia. We have proven that the power dissipated by an ensemble of dispersed magnetic nanoparticles becomes a nonextensive property as a direct consequence of the long-range nature of dipolar interactions. This knowledge is a key point in selecting the correct dose that has to be injected to achieve the desired outcome in intracellular magnetic hyperthermia therapy.