RESUMEN
Core/shell nanostructures based on silica, fluorescent ZnO quantum dots (QDs) and superparamagnetic Fe3O4 nanoparticles (NPs) were prepared and fully characterized by the combination of different techniques and the physical properties of the nanostructures were studied. We demonstrate the efficiency of the atom transfer radical polymerization with activators regenerated by electron transfer process to graft (co-)polymers of different structures and polarity at the surface of metal oxide NPs. The influence of the polymer chain configuration on the optical properties of the ZnO/polymer core/shell QDs was enlightened. Concerning the magnetic properties of the Fe3O4/polymer nanostructures, only the amount of the grafted polymer plays a role on the saturation magnetization of the NPs and no influence of the aggregation was evidenced. The simple and fast process described in this work is efficient for the grafting of copolymers from surfaces and the derived NPs display the combination of the physical properties of the core and the macromolecular behavior of the shell.
RESUMEN
Alginate/gelatin (Alg-Gel) hydrogels have been used experimentally, associated with mesenchymal stromal/stem cells (MSCs), to guide bone tissue formation. One of the main challenges for clinical application is optimizing Alg-Gel stiffness to guide osteogenesis. In this study, we investigated how Alg-Gel stiffness could modulate the dental pulp stem cell (DPSC) attachment, morphology, proliferation, and osteogenic differentiation, identifying the optimal conditions to uncouple osteogenesis from the other cell behaviors. An array of Alg-Gel hydrogels was prepared by casting different percentages of alginate and gelatin cross-linked with 2% CaCl2. We have selected two hydrogels: one with a stiffness of 11 ± 1 kPa, referred to as "low-stiffness hydrogel", formed by 2% alginate and 8% gelatin, and the other with a stiffness of 55 ± 3 kPa, referred to as "high-stiffness hydrogel", formed by 8% alginate and 12% gelatin. Hydrogel analyses showed that the average swelling rates were 20 ± 3% for the low-stiffness hydrogels and 35 ± 2% for the high-stiffness hydrogels. The degradation percentage was 47 ± 5% and 18 ± 2% for the low- and high-stiffness hydrogels, respectively. Both hydrogel types showed homogeneous surface shape and protein (Alg-Gel) interaction with CaCl2 as assessed by physicochemical characterization. Cell culture showed good adhesion of the DPSCs to the hydrogels and proliferation. Furthermore, better osteogenic activity, determined by ALP activity and ARS staining, was obtained with high-stiffness hydrogels (8% alginate and 12% gelatin). In summary, this study confirms the possibility of characterizing and optimizing the stiffness of Alg-Gel gel to guide osteogenesis in vitro without altering the other cellular properties of DPSCs.
RESUMEN
Designing and manufacturing multifunctional nanoparticles (NPs) are of considerable interest for both academic and industrial research. Among NPs used in this field, iron oxide NPs show low toxicity compared to metallic ones and are thus of high interest for biomedical applications. In this work, superparamagnetic Fe3-δO4-based core/shell NPs were successfully prepared and characterized by the combination of different techniques, and their physical properties were investigated. We demonstrate the efficiency of the layer-by-layer process to graft polyelectrolytes on the surface of iron oxide NPs. The influence of the polyelectrolyte chain configuration on the magnetic properties of the Fe3-δO4/polymer core/shell NPs was enlightened. The simple and fast process described in this work is efficient for the grafting of polyelectrolytes from surfaces, and thus, derived Fe3-δO4 NPs display both the physical properties of the core and of the macromolecular shell. Finally, the cytotoxicity toward the human THP-1 monocytic cell line of the core/shell NPs was assessed. The results showed that the polymer-capped Fe3-δO4 NPs exhibited almost no toxicity after 24 h of exposure at concentrations up to 25 µg mL-1. Our results show that these smart superparamagnetic nanocarriers with stealth properties are promising for applications in multimodal cancer therapy, including drug delivery.
RESUMEN
This study reports on the development of thermoresponsive core/shell magnetic nanoparticles (MNPs) based on an iron oxide core and a thermoresponsive copolymer shell composed of 2-(2-methoxy)ethyl methacrylate (MEO2MA) and oligo(ethylene glycol)methacrylate (OEGMA) moieties. These smart nano-objects combine the magnetic properties of the core and the drug carrier properties of the polymeric shell. Loading the anticancer drug doxorubicin (DOX) in the thermoresponsive MNPs via supramolecular interactions provides advanced features to the delivery of DOX with spatial and temporal controls. The so coated iron oxide MNPs exhibit superparamagnetic behavior with a saturation magnetization of around 30 emu g-1. Drug release experiments confirmed that only a small amount of DOX was released at room temperature, while almost 100% drug release was achieved after 52 h at 42 °C with Fe3-δO4@P(MEO2MA60OEGMA40), which grafted polymer chains displaying a low critical solution temperature of 41 °C. Moreover, the MNPs exhibit magnetic hyperthermia properties as shown by specific absorption rate measurements. Finally, the cytotoxicity of the core/shell MNPs toward human ovary cancer SKOV-3 cells was tested. The results showed that the polymer-capped MNPs exhibited almost no toxicity at concentrations up to 12 µg mL-1, whereas when loaded with DOX, an increase in cytotoxicity and a decrease of SKOV-3 cell viability were observed. From these results, we conclude that these smart superparamagnetic nanocarriers with stealth properties are able to deliver drugs to tumor and are promising for applications in multimodal cancer therapy.
Asunto(s)
Doxorrubicina , Portadores de Fármacos , Calor , Hipertermia Inducida , Nanopartículas de Magnetita , Neoplasias , Línea Celular Tumoral , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacocinética , Preparaciones de Acción Retardada/farmacología , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacología , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacología , Humanos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapéutico , Neoplasias/metabolismo , Neoplasias/patología , Neoplasias/terapiaRESUMEN
The unique physical properties of the superparamagnetic nanoparticles (SPIONs) have made them candidates of choice in nanomedicine especially for diagnostic imaging, therapeutic applications and drug delivery based systems. In this study, superparamagnetic Fe3O4 NPs were synthesized and functionalized with a biocompatible thermoresponsive copolymer to obtain temperature responsive core/shell NPs. The ultimate goal of this work is to build a drug delivery system able to release anticancer drugs in the physiological temperatures range. The core/shell NPs were first synthesized and their chemical, physical, magnetic and thermo-responsive properties where fully characterized in a second step. The lower critical solution temperature (LCST) of the core/shell NPs was tuned in physiological media in order to release the cancer drug at a controlled temperature slightly above the body temperature to avoid any premature release of the drug. The core/shell NPs exhibiting the targeted LCST were then loaded with Doxurubicin (DOX) and the drug release properties were then studied with the temperature. Moreover the cytotoxicity tests have shown that the core/shell NPs had a very limited cytotoxicity up to concentration of 25µg/mL. This investigation showed that the significant release occurred at the targeted temperature in the physiological media making those nano-systems very promising for further use in drug delivery platform.