Magnetic Nanoemulsions for the Intra-Articular Delivery of Ascorbic Acid and Dexamethasone.

(1) Osteoarthritis (OA) is a progressive joint degenerative disease that currently has no cure. Limitations in the development of innovative disease modifying therapies are related to the complexity of the underlying pathogenic mechanisms. In addition, there is the unmet need for efficient drug delivery methods. Magnetic nanoparticles (MNPs) have been proposed as an efficient modality for the delivery of bioactive molecules within OA joints, limiting the side effects associated with systemic delivery. We previously demonstrated MNP's role in increasing cell proliferation and chondrogenesis. In the design of intra-articular therapies for OA, the combined NE-MNP delivery system could provide increased stability and biological effect. (2) Proprietary Fe3O4 MNPs formulated as oil-in-water (O/W) magneto nanoemulsions (MNEs) containing ascorbic acid and dexamethasone were tested for size, stability, magnetic properties, and in vitro biocompatibility with human primary adipose mesenchymal cells (ADSC), cell mobility, and chondrogenesis. In vivo biocompatibility was tested after systemic administration in mice. (3) We report high MNE colloidal stability, magnetic properties, and excellent in vitro and in vivo biocompatibility. By increasing ADSC migration potential and chondrogenesis, MNE carrying dexamethasone and ascorbic acid could reduce OA symptoms while protecting the cartilage layer.

Magnetic Nanoparticle Coating Decreases the Senescence and Increases the Targeting Potential of Fibroblasts and Adipose-Derived Mesenchymal Stem Cells.

Magnetic nanoparticles (MNPs) are intensely scrutinized for applications in emerging biomedical fields. Their potential use for drug delivery, tracking, and targeting agents or for cell handling is tested for regenerative medicine and tissue engineering applications. The large majority of MNPs tested for biomedical use are coated with different lipids and natural or synthetic polymers in order to decrease their degradation process and to increase the ability to transport drugs or bioactive molecules. Our previous studies highlighted the fact that the as-prepared MNP-loaded cells can display increased resistance to culture-induced senescence as well as ability to target pathological tissues; however, this effect tends to be dependent on the cell type. Here, we assessed comparatively the effect of two types of commonly used lipid coatings, oleic acid (OA) and palmitic acid (PA), on normal human dermal fibroblasts and adipose-derived mesenchymal cells with culture-induced senescence and cell motility in vitro. OA and PA coatings improved MNPs stability and dispersibility. We found good viability for cells loaded with all types of MNPs; however, a significant increase was obtained with the as-prepared MNPs and OA-MNPs. The coating decreases iron uptake in both cell types. Fibroblasts (Fb) integrate MNPs at a slower rate compared to adipose-derived mesenchymal stem cells (ADSCs). The as-prepared MNPs induced a significant decrease in beta-galactosidase (B-Gal) activity with a nonsignificant one observed for OA-MNPs and PA-MNPs in ADSCs and Fb. The as-prepared MNPs significantly decrease senescence-associated B-Gal enzymatic activity in ADSCs but not in Fb. Remarkably, a significant increase in cell mobility could be detected in ADSCs loaded with OA-MNPscompared to controls. The OA-MNPs uptake significantly increases ADSCs mobility in a wound healing model in vitro compared to nonloaded counterparts, while these observations need to be validated in vivo. The present findings provide evidence that support applications of OA-MNPs in wound healing and cell therapy involving reparative processes as well as organ and tissue targeting.

Flash-cooling assisted sol-gel self-ignited synthesis of magnetic carbon dots-based heterostructure with antitumor properties.

This work addresses current direction of the nanoparticles-based systems intended for cancer therapy by developing a newly-formulated innovative chemically-engineered anti-tumor composite consisting in a magnetic, fluorescent, lipophilic, and biologically-active carbon heterostructure capable by itself or through coupling with a chemotherapeutic agent to selectively induce tumor cell death. The anti-tumor compound was synthesized through a modified sol-gel method by addition of a low-cost molecule with recently proven anti-tumor properties which was combusted and flash-cooled along with magnetic iron oxides precursors at 250 °C. The synthesized compound consisted in carbon dots, graphene and hematite nanoparticles which endowed the composite with unique simultaneous fluorescence, magnetic and anti-tumor properties. The in-vitro cytotoxicity performed on tumor cells (human osteosarcoma) and normal cells (fibroblasts) showed a selective cytotoxic effect induced after 24 h of treatment by the drug-free composite, leading to a cell death of 37%, for a composite concentration of 0.01 mg/mL per 104 tumor cells, whereas the composite loaded with an antitumor drug (mitoxantrone) boosted the cell death effect to 47% for similar exposure conditions. The method shows high potential as it boosts drug transfer within tumor cells. Different antitumor drugs already in clinical use can be used following their separate or in-cocktail controlled combustion.

The effect of magnetic field exposure on differentiation of magnetite nanoparticle-loaded adipose-derived stem cells.

Magnetic nanoparticles (MNPs) are versatile tools for various applications in biotechnology and nanomedicine. MNPs-mediated cell tracking, targeting and imaging are increasingly studied for regenerative medicine applications in cell therapy and tissue engineering. Mechanical stimulation influences mesenchymal stem cell differentiation. Here we show that MNPs-mediated magneto-mechanical stimulation of human primary adipose derived stem cells (ADSCs) exposed to variable magnetic field (MF) influences their adipogenic and osteogenic differentiation. ADSCs loaded with biocompatible magnetite nanoparticles of 6.6 nm, and with an average load of 21 picograms iron/cell were exposed to variable low intensity (0.5 mT - LMF) and higher intensity magnetic fields (14.7 and 21.6 mT - HMF). Type, duration, intensity and frequency of MF differently affect differentiation. Short time (2 days) intermittent exposure to LMF increases adipogenesis while longer (7 days) intermittent as well as continuous exposure favors osteogenesis. HMF (21.6 mT) short time intermittent exposure favors osteogenesis. Different exposure protocols can be used to increase differentiation dependently on expected results. Magnetic remotely-actuated MNPs up-taken by ADSCs promotes the shift towards osteoblastic lineage. ADSCs-MNPs under MF exposure could be used for enabling osteoblastic conversion during cell therapy for systemic osteoporosis. Current results enable further in vivo studies investigating the role of remotely-controlled magnetically actuated ADSCs-MNPs for the treatment of osteoporosis.