Aspartic Acid Stabilized Iron Oxide Nanoparticles for Biomedical Applications.

Aspartic acid stabilized iron oxide nanoparticles (A-IONPs) with globular shape and narrow size distribution were prepared by the co-precipitation method in aqueous medium. A quantum-mechanical approach to aspartic acid optimized structure displayed negative charged sites, relatively high dipole moment, and hydrophilicity, which recommended it for interaction with iron cations and surrounding water electrical dipoles. A-IONPs were characterized by TEM, XRD, ATR-FTIR, EDS, DSC, TG, DLS, NTA, and VSM techniques. Theoretical study carried out by applying Hartree-Fock and density functional algorithms suggested that some aspartic acid properties related to the interaction can develop with nanoparticles and water molecules. The results of experimental investigation showed that the mean value of particle physical diameters was 9.17 ± 2.2 nm according to TEM image analysis, the crystallite size was about 8.9 nm according to XRD data, while the magnetic diameter was about 8.8 nm, as was determined from VSM data interpretation with Langevin's theory. The A-IONP suspension was characterized by zeta-potential of about -11.7 mV, while the NTA investigation revealed a hydrodynamic diameter of 153.9 nm. These results recommend the A-IONP suspension for biomedical applications.

Magnetic nanoparticle loaded human adipose derived mesenchymal cells spheroids in levitated culture.

Magnetic nanoparticles (MNP) are intensely scrutinized for biomedical applications due to their excellent biocompatibility and adjustable magnetic field (MF) responsiveness. Three-dimensional spheroid culture of ADSC improves stem cell proliferation and differentiation, increasing their potential for clinical applications. In this study we aimed to detect if MF levitated culture of ADSC loaded with proprietary MNP maintain the properties of ADSC and improve their performances. Levitated ADSC-MNP formed aggregates with increased volume and reduced number compared to nonlevitated ones. ADSC-MNP from levitated spheroid displayed higher viability, proliferation and mobility compared to nonlevitated and 2D culture. Levitated and nonlevitated ADSC-MNP spheroids underwent three lineage differentiation, demonstrating preserved ADSC stemness. Quantitative osteogenesis showed similar values in MNP-loaded levitated and nonlevitated spheroids. Significant increases in adipogenic conversion was observed for all 3D formulation. Chondrogenic conversion in levitated and nonlevitated spheroids produced comparable ratio glucosaminoglycan (GAG)/DNA. Increased chondrogenesis could be observed for ADSC-MNP in both levitated and nonlevitated condition. Taken together, ADSC-MNP levitated spheroids retain stemness and display superior cell viability and migratory capabilities. Furthermore, the method consistently increases spheroid maneuverability, potentially facilitating large scale manufacturing and automation. Levitated spheroid culture of ADSC-MNP can be further tested for various application in regenerative medicine and organ modeling.

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.

Human adipose-derived stem cells loaded with drug-coated magnetic nanoparticles for in-vitro tumor cells targeting.

Magnetic nanoparticles (MNPs) functionalized with different therapeutics delivered by mesenchymal stem cells represent a promising approach to improve the typical drug delivery methods. This innovative method, based on the "Trojan horse" principle, faces however important challenges related to the viability of the MNPs-loaded cells and drug stability. In the present study we report about an in vitro model of adipose-derived stem cells (ADSCs) loaded with palmitate-coated MNPs (MNPsPA) as antitumor drug carriers targeting a 3D tissue-like osteosarcoma cells. Cell viability, MNPsPA-drug loading capacity, cell speed, drug release rate, magnetization and zeta potential were determined and analysed. The results revealed that ADSCs loaded with MNPsPA-drug complexes retained their viability at relatively high drug concentrations (up to 1.22 pg antitumor drug/cell for 100% cell viability) and displayed higher speed compared to the targeted tumor cells in vitro. The magnetization of the sterilized MNPsPA complexes was 67 emu/g within a magnetic field corresponding to induction values of clinical MRI devices. ADSCs payload was around 9 pg magnetic material/cell, with an uptake rate of 6.25 fg magnetic material/min/cell. The presented model is a proof-of-concept platform for stem cells-mediated MNPs-drug delivery to solid tumors that could be further correlated with MRI tracking and magnetic hyperthermia for theranostic applications.