Enhancement of chemotherapy effects by non-lethal magneto-mechanical actuation of gold-coated magnetic nanoparticles.

Remote magneto-mechanical actuation (MMA) of magnetic nanoparticles (MNP) is emerging as a promising therapy method in oncology. However, translation to the clinic faces the challenge of whole-body action and the reluctance about indiscriminate mechanical action of the nanoparticles on tumor and healthy cells. Here, we show how the MMA method based on magnetically-rotated gold-coated MNP boosts only the activity of an unbound antitumor drug, without physical damage of cells via MNP. Therefore, in clinical practice, the effect of antitumor drug can be safely increased systemically while maintaining drug concentrations at current doses.

Fe-Cr-Nb-B Magnetic Particles and Adipose-Derived Mesenchymal Cells Trigger Cancer Cell Apoptosis by Magneto-Mechanical Actuation.

Magnetic nanoparticles (MPs) are emerging as powerful and versatile tools for biotechnology, including cancer research and theranostic applications. Stem cell-mediated magnetic particle delivery has been previously recognized as a modality to target sites of malignancies. Here, we propose the use of adipose-derived mesenchymal cells (ADSC) for the targeted delivery of Fe-Cr-Nb-B magnetic particles to human osteosarcoma (HOS) cells and magneto-mechanical actuation (MMA) for targeting and destroying HOS cells. We show that MPs are easily incorporated by ADSCs and HOS cells, as confirmed by TEM images and a ferrozine assay. MP-loaded ADSCs display increased motility towards tumor cells compared with their unloaded counterparts. MMA of MP-loaded ADSCs induces HOS destruction, as confirmed by the MTT and live/dead assays. MMA enables the release of the MPs towards cancer cells, producing a significant decrease (about 80%) in HOS viability immediately after application. In contrast, normal human dermal fibroblasts' (NHDFs) viability exposed to similar conditions remains high, showing a differential behavior of normal and malignant cells to MP load and MMA exposure. Taken together, the method could derive successful strategies for in vivo applications in targeting and destroying malignant cells while protecting normal cells.

Wild-Grown Romanian Helleborus purpurascens Approach to Novel Chitosan Phyto-Nanocarriers-Metabolite Profile and Antioxidant Properties.

The current nanomedicinal approach combines medicinal plants and nanotechnology to create new scaffolds with enhanced bioavailability, biodistribution and controlled release. In an innovative approach to herb encapsulation in nanosized chitosan matrices, wild-grown Romanian Helleborus purpurascens was used to prepare two new chitosan nanocarriers. The first carrier preparation involved the nanoencapsulation of hellebore in chitosan. The second carrier emerged from two distinct stages: hellebore-AgNPs phyto-carrier system succeeded by nanoencapsulation in chitosan. The morphostructural characteristics and thermal behavior of these newly prepared nanocarriers were examined using FT-IR, XRD, DLS, SEM, EDS and thermogravimetric analyses. In addition, the encapsulation yield, encapsulation efficiency and encapsulation contents were investigated. The antioxidant activity was estimated using four in vitro, noncompetitive methods: total phenolic assay; 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay; phosphomolybdate (i.e., total antioxidant capacity); and iron(III)-phenanthroline antioxidant assay. Moreover, this study reports the first low-molecular-weight metabolite profile of wild-grown Romanian Helleborus purpurascens Waldst. & Kit. A total of one hundred and five secondary metabolites were identified in the mass spectra (MS)-positive mode from fourteen secondary metabolite categories (alkaloids, butenolides, bufadienolides, phytoecdysteroids, amino acids and peptides, terpenoids, fatty acids, flavonoids, phenolic acids, sterols, glycosides, carbohydrates, nucleosides and miscellaneous). The collective results suggest the potential application is a promising new antioxidant vehicle candidate in tumor therapeutic strategy.

Innovative Low-Cost Composite Nanoadsorbents Based on Eggshell Waste for Nickel Removal from Aqueous Media.

In a contemporary sustainable economy, innovation is a prerequisite to recycling waste into new efficient materials designed to minimize pollution and conserve non-renewable natural resources. Using an innovative approach to remediating metal-polluted water, in this study, eggshell waste was used to prepare two new low-cost nanoadsorbents for the retrieval of nickel from aqueous solutions. Scanning electron microscopy (SEM) results show that in the first eggshell-zeolite (EZ) adsorbent, the zeolite nanoparticles were loaded in the eggshell pores. The preparation for the second (iron(III) oxide-hydroxide)-eggshell-zeolite (FEZ) nanoadsorbent led to double functionalization of the eggshell base with the zeolite nanoparticles, upon simultaneous loading of the pores of the eggshell and zeolite surface with FeOOH particles. Structural modification of the eggshell led to a significant increase in the specific surface, as confirmed using BET analysis. These features enabled the composite EZ and FEZ to remove nickel from aqueous solutions with high performance and adsorption capacities of 321.1 mg/g and 287.9 mg/g, respectively. The results indicate that nickel adsorption on EZ and FEZ is a multimolecular layer, spontaneous, and endothermic process. Concomitantly, the desorption results reflect the high reusability of these two nanomaterials, collectively suggesting the use of waste in the design of new, low-cost, and highly efficient composite nanoadsorbents for environmental bioremediation.

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.

Untargeted Metabolomic Approach of Curcuma longa to Neurodegenerative Phytocarrier System Based on Silver Nanoparticles.

Curcuma is one of the most famous medicinal and tropical aromatic plants. Its health benefits have been appreciated and exploited in traditional Asian medicine since ancient times. Various studies have investigated its complex chemical composition and demonstrated the remarkable therapeutic properties of curcuma's phytoconstituents. Oxidative stress is a decisive driving factor triggering numerous pathologies (neurodegenerative, psychiatric and cardiovascular diseases; diabetes; tumors, etc.). Numerous recent studies have focused on the use of natural compounds and nanomaterials as innovative molecular targeting agents as effective therapeutic strategies. In this study, we report, for the first time, the development of a simple target phytocarrier system that capitalizes on the bioactive properties of curcuma and AgNPs. The complete metabolic profile of curcuma was determined based on gas chromatography-mass spectrometry (GC-MS) and electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-QTOF-MS). A total of 80 metabolites were identified under mass spectra (MS)-positive mode from 10 secondary metabolite categories: terpenoids, amino acids, diarylheptanoids, flavonoids, phenolic acids, steroids, fatty acids, coumarins, alkaloids and miscellaneous. In addition, the biological activity of each class of metabolites was discussed. A comprehensive characterization (FT-IR, UV-Vis, DLS, SEM, TEM, EDS, zeta potential and XRD) was performed to study the morphostructural properties of this new phytocarrier system. Antioxidant activity of the new phytocarrier system was evaluated using a combination of in vitro methods (total phenolic assay, 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and cyclic voltammetric method (Trolox equivalent antioxidant capacity (TEAC) electrochemical assay)). Antioxidants assays showed that the phytocarrier system exhibits superior antioxidant properties to those of its components, i.e., curcuma or citrate-coated-AgNPs. These data confirm the potential to enhance relevant theoretical knowledge in the area of innovative antioxidant agents, with potential application in neurodegenerative therapeutic strategies.

Magnetic nanowires substrate increases adipose-derived mesenchymal cells osteogenesis.

Magnetic nanomaterials are increasingly impacting the field of biology and medicine. Their versatility in terms of shape, structure, composition, coating, and magnetic responsivity make them attractive for drug delivery, cell targeting and imaging. Adipose derived-mesenchymal cells (ASCs) are intensely scrutinized for tissue engineering and regenerative medicine. However, differentiation into musculoskeletal lineages can be challenging. In this paper, we show that uncoated nickel nanowires (Ni NW) partially released from their alumina membrane offer a mechanically-responsive substrate with regular topography that can be used for the delivery of magneto-mechanical stimulation. We have used a tailored protocol for improving ASCs adherence to the substrate, and showed that cells retain their characteristic fibroblastic appearance, cytoskeletal fiber distribution and good viability. We report here for the first time significant increase in osteogenic but not adipogenic differentiation of ASCs on Ni NW exposed to 4 mT magnetic field compared to non-exposed. Moreover, magnetic actuation is shown to induce ASCs osteogenesis but not adipogenesis in the absence of external biochemical cues. While these findings need to be verified in vivo, the use of Ni NW substrate for inducing osteogenesis in the absence of specific differentiation factors is attractive for bone engineering. Implant coating with similar surfaces for orthopedic and dentistry could be as well envisaged as a modality to improve osteointegration.

Romanian Viscum album L.-Untargeted Low-Molecular Metabolomic Approach to Engineered Viscum-AuNPs Carrier Assembly.

Viscum is one of the most famous and appreciated medicinal plants in Europe and beyond. The symbiotic relationship with the host tree and various endogenous and ecological aspects are the main factors on which the viscum metabolites' profiles depend. In addition, European traditional medicine mentions that only in two periods of the year (summer solstice and winter solstice) the therapeutic potential of the plant is at its maximum. Many studies have investigated the phytotherapeutic properties of viscum grown on different species of trees. However, studies on Romanian viscum are relatively few and refer mainly to the antioxidant and antiproliferative activity of mistletoe grown on Acer campestre, Fraxinus excelsior, Populus nigra, Malus domestica, or Robinia pseudoacacia. This study reports the first complete low-molecular-weight metabolite profile of Romanian wild-grown European viscum. A total of 140 metabolites were identified under mass spectra (MS) positive mode from 15 secondary metabolite categories: flavonoids, amino acids and peptides, terpenoids, phenolic acids, fatty acids, organic acids, nucleosides, alcohols and esters, amines, coumarins, alkaloids, lignans, steroids, aldehydes, and miscellaneous. In addition, the biological activity of each class of metabolite is discussed. The development of a simple and selective phyto-engineered AuNPs carrier assembly is reported and an evaluation of the nanocarrier system's morpho-structure is performed, to capitalize on the beneficial properties of viscum and AuNPs.

Fe-Cr-Nb-B Ferrofluid for Biomedical Applications.

A ferrofluid based on Fe67.2Cr12.5Nb0.3B20 magnetic particles with a low Curie temperature was prepared. The particles, most of which had dimensions under 60 nm, were dispersed in a calcium gluconate solution, leading to a stable ferrofluid. The obtained ferrofluid had a magnetization of 0.04 to 0.17 emu/cm3, depending on the particles' concentration, and a viscosity that increased nonlinearly with the applied magnetic field. The ferrofluid appeared to be biocompatible, as it showed low cytotoxicity, even at high concentrations and for long intervals of co-incubation with human cells, demonstrating a good potential to be used for cancer therapies through magnetic hyperthermia as well as magneto-mechanical actuation.

A Simple Protocol for Sample Preparation for Scanning Electron Microscopic Imaging Allows Quick Screening of Nanomaterials Adhering to Cell Surface.

Preparing biological specimens for scanning electron microscopy (SEM) can be difficult to implement, as it requires specialized equipment and materials as well as the training of dedicated personnel. Moreover, the procedure often results in damage to the samples to be analyzed. This work presents a protocol for the preparation of biological samples to evaluate the adherence of nanomaterials on the cell surface using SEM. To this end, we used silicon wafers as a substrate to grow cells and replaced difficult steps such as the critical point drying of the samples in order to make the method quicker and easier to perform. The new protocol was tested using two different types of cells, i.e., human osteosarcoma cells and adipose-derived mesenchymal stem cells, and it proved that it can grossly preserve cell integrity in order to be used to estimate nanomaterials' interaction with cell surfaces.

Magnetic Nanoparticles and Magnetic Field Exposure Enhances Chondrogenesis of Human Adipose Derived Mesenchymal Stem Cells But Not of Wharton Jelly Mesenchymal Stem Cells.

Purpose: Iron oxide based magnetic nanoparticles (MNP) are versatile tools in biology and medicine. Adipose derived mesenchymal stem cells (ADSC) and Wharton Jelly mesenchymal stem cells (WJMSC) are currently tested in different strategies for regenerative regenerative medicine (RM) purposes. Their superiority compared to other mesenchymal stem cell consists in larger availability, and superior proliferative and differentiation potential. Magnetic field (MF) exposure of MNP-loaded ADSC has been proposed as a method to deliver mechanical stimulation for increasing conversion to musculoskeletal lineages. In this study, we investigated comparatively chondrogenic conversion of ADSC-MNP and WJMSC with or without MF exposure in order to identify the most appropriate cell source and differentiation protocol for future cartilage engineering strategies. Methods: Human primary ADSC and WJMSC from various donors were loaded with proprietary uncoated MNP. The in vitro effect on proliferation and cellular senescence (beta galactosidase assay) in long term culture was assessed. In vitro chondrogenic differentiation in pellet culture system, with or without MF exposure, was assessed using pellet histology (Safranin O staining) as well as quantitative evaluation of glycosaminoglycan (GAG) deposition per cell. Results: ADSC-MNP complexes displayed superior proliferative capability and decreased senescence after long term (28 days) culture in vitro compared to non-loaded ADSC and to WJMSC-MNP. Significant increase in chondrogenesis conversion in terms of GAG/cell ratio could be observed in ADSC-MNP. MF exposure increased glycosaminoglycan deposition in MNP-loaded ADSC, but not in WJMSC. Conclusion: ADSC-MNP display decreased cellular senescence and superior chondrogenic capability in vitro compared to non-loaded cells as well as to WJMSC-MNP. MF exposure further increases ADSC-MNP chondrogenesis in ADSC, but not in WJMSC. Loading ADSC with MNP can derive a successful procedure for obtaining improved chondrogenesis in ADSC. Further in vivo studies are needed to confirm the utility of ADSC-MNP complexes for cartilage engineering.

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.

Fly Ash Coated with Magnetic Materials: Improved Adsorbent for Cu (II) Removal from Wastewater.

Fly ash/magnetite material was used for the adsorption of copper ions from synthetic wastewater. The obtained material was characterized by scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDAX), X-ray diffractometer (XRD), Fourier transform infrared spectroscopy (FTIR), Brunauer-Emmett-Teller (BET) surface area, and vibrating sample magnetometer (VSM). Batch adsorption experiments were employed in order to investigate the effects of adsorbent dose, initial Cu (II) concentration and contact time over adsorption efficiency. The experimental isotherms were modeled using Langmuir (four types of its linearization), Freundlich, Temkin, and Harkins-Jura isotherm models. The fits of the results are estimated according to the Langmuir isotherm, with a maximum adsorption capacity of 17.39 mg/g. The pseudo-second-order model was able to describe kinetic results. The data obtained throughout the study prove that this novel material represents a potential low-cost adsorbent for copper adsorption with improved adsorption capacity and magnetic separation capability compared with raw fly ash.

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.

Comparative effects of magnetic and water-based hyperthermia treatments on human osteosarcoma cells.

INTRODUCTION: Hyperthermia (HT) based on magnetic nanoparticles (MNPs) represents a promising approach to induce the apoptosis/necrosis of tumor cells through the heat generated by MNPs submitted to alternating magnetic fields. However, the effects of temperature distribution on the cancer cells' viability as well as heat resistance of various tumor cell types warrant further investigation. METHODS: In this work, the effects induced by magnetic hyperthermia (MHT) and conventional water-based hyperthermia (WHT) on the viability of human osteosarcoma cells at different temperatures (37°C-47°C) was comparatively investigated. Fe-Cr-Nb-B magnetic nanoparticles were submitted either to alternating magnetic fields or to infrared radiation generated by a water-heated incubator. RESULTS: In terms of cell viability, significant differences could be observed after applying the two HT treatment methods. At about equal equilibrium temperatures, MHT was on average 16% more efficient in inducing cytotoxicity effects compared to WHT, as assessed by MTT cytotoxicity assay. CONCLUSION: We propose the phenomena can be explained by the significantly higher cytotoxic effects initiated during MHT treatment in the vicinity of the heat-generating MNPs compared to the effects triggered by the homogeneously distributed temperature during WHT. These in vitro results confirm other previous findings regarding the superior efficiency of MHT over WHT and explain the cytotoxicity differences observed between the two antitumor HT methods.

Stem cells as delivery vehicles for regenerative medicine-challenges and perspectives.

The use of stem cells as carriers for therapeutic agents is an appealing modality for targeting tissues or organs of interest. Combined delivery of cells together with various information molecules as therapeutic agents has the potential to enhance, modulate or even initiate local or systemic repair processes, increasing stem cell efficiency for regenerative medicine applications. Stem-cell-mediated delivery of genes, proteins or small molecules takes advantage of the innate capability of stem cells to migrate and home to injury sites. As the native migratory properties are affected by in vitro expansion, the existent methods for enhancing stem cell targeting capabilities (modified culture methods, genetic modification, cell surface engineering) are described. The role of various nanoparticles in equipping stem cells with therapeutic small molecules is revised together with their class-specific advantages and shortcomings. Modalities to circumvent common challenges when designing a stem-cell-mediated targeted delivery system are described as well as future prospects in using this approach for regenerative medicine applications.

Human Adipose Derived Stem Cells and Osteoblasts Interaction with Fe-Cr-Nb-B Magnetic Nanoparticles.

The use of materials at nanoscale is currently of increasing interest for life sciences and medicine. Magnetic nanoparticles (MNPs) are under scrutiny for a large array of applications in nanomedicine as diagnostic and therapeutic tools. Proprietary Fe-Cr-Nb-B MNPs display heating properties that recommends them as potent agents for delivery of local hyperthermia for the treatment of solid tumours. Stem cell mediated delivery represents a safe and accurate modality to target remote or metastatic tumour sites. In this study we investigated the interaction of Fe-Cr-Nb-B nanoparticles with human adipose derived mesenchymal stem cells and human primary osteoblasts. We found that: (a) bare and chitosan coated Fe-Cr-Nb-B are internalized by both cell types, (b) they can be detected up to 28 days inside the cells without signs of membrane disruption and (c) they do not display in vitro toxicity. MNPs are uploaded by cells in a time dependent manner with maximum uptake after 7-8 days cell-particle incubation. Particle internalization do not interfere with proliferative and differentiation potential (osteogenesis and adipogenesis) demonstrating an unaltered cellular phenotype. Further investigation of the potential effect of MNPs internalization on cytoskeleton dynamics and in inducing oxidative stress will be required as it is of interest for predicting cell migration and survival after transplantation. Present results are encouraging for designing a stemcell mediated delivery of Fe-Cr-Nb-B magnetic nanoparticles to solid tumour sites for hyperthermia applications.