RESUMEN
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.
RESUMEN
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 1.22â¯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 67â¯emu/g within a magnetic field corresponding to induction values of clinical MRI devices. ADSCs payload was around 9â¯pg magnetic material/cell, with an uptake rate of 6.25â¯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.
Asunto(s)
Tejido Adiposo/citología , Nanopartículas de Magnetita/química , Osteosarcoma/patología , Células Madre/citología , Muerte Celular , Movimiento Celular , Liberación de Fármacos , Dispersión Dinámica de Luz , Humanos , Campos Magnéticos , Nanopartículas de Magnetita/ultraestructuraRESUMEN
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.
Asunto(s)
Hipertermia Inducida/métodos , Magnetismo , Osteosarcoma/terapia , Agua/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Rayos Infrarrojos , Campos Magnéticos , Nanopartículas/química , TemperaturaRESUMEN
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.