RESUMEN
Primary bone cancers commonly involve surgery to remove the malignant tumor, complemented with a postoperative treatment to prevent cancer resurgence. Studies on magnetic hyperthermia, used as a single treatment or in synergy with chemo- or radiotherapy, have shown remarkable success in the past few decades. Multifunctional biomaterials with bone healing ability coupled with hyperthermia property could thus be of great interest to repair critical bone defects resulting from tumor resection. For this purpose, we designed superparamagnetic and bioactive nanoparticles (NPs) based on iron oxide cores (γ-Fe2O3) encapsulated in a bioactive glass (SiO2-CaO) shell. Nanometric heterostructures (122 ± 12 nm) were obtained through a two-step process: co-precipitation of 16 nm sized iron oxide NPs, followed by the growth of a bioactive glass shell via a modified Stöber method. Their bioactivity was confirmed by hydroxyapatite growth in simulated body fluid, and cytotoxicity assays showed they induced no significant death of human mesenchymal stem cells after 7 days. Calorimetric measurements were carried out under a wide range of alternating magnetic field amplitudes and frequencies, considering clinically relevant parameters, and some were made in viscous medium (agar) to mimic the implantation conditions. The experimental specific loss power was predictable with respect to the Linear Response Theory, and showed a maximal value of 767 ± 77 W gFe-1 (769 kHz, 23.9 kA m-1 in water). An interesting value of 166 ± 24 W gFe-1 was obtained under clinically relevant conditions (157 kHz, 23.9 kA m-1) for the heterostructures immobilized in agar. The good biocompatibility, bioactivity and heating ability suggest that these γ-Fe2O3@SiO2-CaO NPs are a promising biomaterial to be used as it is or included in a scaffold to heal bone defects resulting from bone tumor resection.
Asunto(s)
Neoplasias Óseas , Hipertermia Inducida , Osteosarcoma , Agar , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Neoplasias Óseas/terapia , Vidrio/química , Humanos , Fenómenos Magnéticos , Dióxido de SilicioRESUMEN
The past few decades have seen the development of new bone cancer therapies, triggered by the discovery of new biomaterials. When the tumoral area is small and accessible, the common clinical treatment implies the tumor mass removal followed by bone reconstruction or consolidation with a bioceramic or a metallic scaffold. Even though the treatment also involves chemotherapy or radiotherapy, resurgence of cancer cells remains possible. We have thus designed a new kind of heterostructured nanobiomaterial, composed of SiO2-CaO bioactive glass as the shell and superparamagnetic γ-Fe2O3 iron oxide as the core in order to combine the benefits of bone repair thanks to the glass bioactivity and cancer cell destruction through magnetic hyperthermia. These multifunctional core-shell nanoparticles (NPs) have been obtained using a two-stage procedure, involving the coprecipitation of 11 nm sized iron oxide NPs followed by their encapsulation inside a bioactive glass shell by sol-gel chemistry. The as-produced spherical multicore-shell NPs show a narrow size distribution of 73 ± 7 nm. Magnetothermal loss measurements by calorimetry under an alternating magnetic field and in vitro bioactivity assessment performed in simulated body fluid showed that these heterostructures exhibit a good heating capacity and a fast mineralization process (hydroxyapatite forming ability). In addition, their in vitro cytocompatibility, evaluated in the presence of human mesenchymal stem cells during 3 and 7 days, has been demonstrated. These first findings suggest that γ-Fe2O3@SiO2-CaO heterostructures are a promising biomaterial to fill bone defects resulting from bone tumor resection, as they have the ability to both repair bone tissue and act as thermoseeds for cancer therapy.
Asunto(s)
Antineoplásicos/uso terapéutico , Materiales Biocompatibles/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Células Madre Mesenquimatosas/efectos de los fármacos , Nanopartículas/química , Antineoplásicos/química , Materiales Biocompatibles/química , Compuestos de Calcio/química , Células Cultivadas , Óxido Ferrosoférrico/química , Humanos , Óxidos/química , Tamaño de la Partícula , Dióxido de Silicio/química , Propiedades de SuperficieRESUMEN
Sol-gel-derived bioactive glass nanoparticles (BGNs) are fascinating materials for bone regeneration. In the literature, it can be found that their specific surface area and their calcium content (Ca/Si ratio) are the two key parameters impacting strongly the particles' bioactivity. Nevertheless, in most studies, in vitro bioactivity tests are performed on a series of materials where both the composition and the specific surface area are varied. It is thus difficult to unravel the effect of each parameter independently. In this study, spherical and monodispersed BGNs with different Ca/Si ratios and a similar specific surface area have been synthesized by a modified Stöber method in order to specify the impact of the calcium content only. The mineralization studies performed in simulated body fluid showed that the bioactivity increases with the amount of calcium incorporated in the glass matrix. However, this effect is not significant in the composition interval studied (7-15% mol of CaO). Such a result proves that the effective Ca/Si ratio is not the major parameter that affects the bioactivity of sol-gel binary BGs. In vitro biocompatibility assessment during 3 and 7 days using human mesenchymal stem cells in contact with the sample showing the fastest mineralization proved its noncytotoxicity. Hence, biomedical applications can be intended for this sample.
RESUMEN
The aim of this study was to investigate the effect of three synthesis parameters on the morphology and composition of nanosized binary bioactive glass particles (nBGPs) obtained through a modified Stöber process. Syntheses were conducted by varying only one parameter at a time while keeping the other parameters constant. As already mentioned in the literature, the ammonium hydroxide volume conditioned the size of the nanoparticles. Nonagglomerated monodispersed spherical particles with a diameter between 70 and 452 nm were produced. The quantity of calcium nitrate and the moment it was introduced in the sol had a tremendous impact on the quantity of calcium inserted and on the particle morphology and aggregation state. High Ca-content particles were obtained when the calcium precursor addition time was 1 h or less after the beginning of the sol-gel reaction but at the cost of a strong aggregation. A better control on the morphology, polydispersity and dispersibility of the nBGPs was achieved when the Ca(NO3)2 addition time was increased up to 6 h. However, a significant decrease of the quantity of Ca2+ inserted was also noticed. Using an intermediate (3 h) addition time, the quantity of calcium nitrate has been optimized to maximize the insertion of Ca2+ ions inside the silica particles. Finally, an optimum initial Ca/Si atomic ratio of 2, maximizing Ca insertion while limiting the salt quantity used, was found. It led to the synthesis of particles with a molar composition of 0.9SiO2-0.1CaO without any side effect on the particle stability and morphological characteristics.
RESUMEN
Spin crossover cations have been successfully synthesized in the pores of a mesoporous robust Metal-Organic Framework (MOF) MIL-100(Al) through sequential introduction of Fe(iii) cations and a sal2trien ligand. The MIL-100(Al)@Fe(sal2trien) hybrid material retains its crystallinity and partial porosity compared to the parent MOF. The spin state of the Fe(sal2trien)+ cations can be modulated at room temperature through sorption of guest molecules, paving the way to the design of a new generation of sensors based on MOF@spin crossover complex solids.