Elaboration de nanoparticules magnétiques et bioactives pour le traitement du cancer et la régénération de tissus osseux

Most patients suffering of cancer develop bone metastases because of the migration of primary tumors cells. Surgical extraction is one of the commonly used therapies in clinical settings but deteriorates significantly the patient quality of life. In this context, it is needed to improve this therapy to minimize its side effects. We propose to design a new kind of multifunctional biomaterial, composed of bioactive glass and iron oxide nanoparticles to combine the benefits of bone regeneration and destruction of cancerous cells through magnetic hyperthermia. Indeed, these particles could be implanted into the cavity originating from the tumor removal, and the heat produced by the magnetic particles in an alternative magnetic field would destroy selectively the remaining or resurgent cancerous cells. Finally, the bioactive glass would induce the bone regeneration in the cavity. In a first part of this work, the influence of the synthesis parameters (sol-gel process) on the composition and the textural properties of bioactive nanoparticles (SiO2-CaO) have been studied. The impact of their composition on their bioactivity has then been investigated. In a second part, core/shell nanoparticles composed of maghemite (γ-Fe2O3) and bioactive glass (SiO2-CaO) have been synthesized and characterized. The good performances in terms of heating power (SAR) and bioactivity of the γ-Fe2O3@SiO2-CaO heterostructures pave the way to their use for bone cancer treatment.La plupart des patients atteints de cancer développent également des métastases osseuses dues à la migration des cellules tumorales primaires. L’extraction de la masse tumorale par une intervention chirurgicale fait partie des traitements classiques utilisés en milieu clinique, néanmoins elle détériore considérablement la qualité de vie du patient. Dans un tel contexte, il est donc nécessaire d’améliorer cette thérapie afin de minimiser les inconvénients qui y sont associés. Nous proposons l’élaboration d’un biomatériau multifonctionnel, constitué de verre bioactif et de nanoparticules magnétiques en vue de combiner les effets bénéfiques de la régénération osseuse et de la destruction des cellules cancéreuses par hyperthermie magnétique. En effet, après implantation de ces particules dans le défaut osseux généré par l’exérèse de la masse tumorale, la production de chaleur sous champ magnétique alternatif pourrait détruire les cellules cancéreuses restantes ou résurgentes, puis le verre bioactif induirait la minéralisation osseuse dans la cavité. Dans une première partie, l’influence des paramètres de synthèse (voie sol-gel) sur la composition et les propriétés texturales de nanoparticules bioactives (SiO2-CaO) a été étudiée. L’impact de la composition sur leur bioactivité a ensuite été évalué. Dans une deuxième partie, des nanoparticules à structure cœur-coquille composées de maghémite (γ-Fe2O3) et de verre bioactif (SiO2-CaO) ont été synthétisées et caractérisées. Les bonnes performances en termes de pouvoir chauffant (SAR) et de bioactivité des hétérostructures γ-Fe2O3@SiO2-CaO ouvrent la voie pour leur utilisation pour le traitement des tumeurs osseuses

Elaboration of magnetic and bioactive nanoparticles for cancer treatment and bone tissue regeneration

La plupart des patients atteints de cancer développent également des métastases osseuses dues à la migration des cellules tumorales primaires. L’extraction de la masse tumorale par une intervention chirurgicale fait partie des traitements classiques utilisés en milieu clinique, néanmoins elle détériore considérablement la qualité de vie du patient. Dans un tel contexte, il est donc nécessaire d’améliorer cette thérapie afin de minimiser les inconvénients qui y sont associés. Nous proposons l’élaboration d’un biomatériau multifonctionnel, constitué de verre bioactif et de nanoparticules magnétiques en vue de combiner les effets bénéfiques de la régénération osseuse et de la destruction des cellules cancéreuses par hyperthermie magnétique. En effet, après implantation de ces particules dans le défaut osseux généré par l’exérèse de la masse tumorale, la production de chaleur sous champ magnétique alternatif pourrait détruire les cellules cancéreuses restantes ou résurgentes, puis le verre bioactif induirait la minéralisation osseuse dans la cavité. Dans une première partie, l’influence des paramètres de synthèse (voie sol-gel) sur la composition et les propriétés texturales de nanoparticules bioactives (SiO2-CaO) a été étudiée. L’impact de la composition sur leur bioactivité a ensuite été évalué. Dans une deuxième partie, des nanoparticules à structure cœur-coquille composées de maghémite (γ-Fe2O3) et de verre bioactif (SiO2-CaO) ont été synthétisées et caractérisées. Les bonnes performances en termes de pouvoir chauffant (SAR) et de bioactivité des hétérostructures γ-Fe2O3@SiO2-CaO ouvrent la voie pour leur utilisation pour le traitement des tumeurs osseuses.Most patients suffering of cancer develop bone metastases because of the migration of primary tumors cells. Surgical extraction is one of the commonly used therapies in clinical settings but deteriorates significantly the patient quality of life. In this context, it is needed to improve this therapy to minimize its side effects. We propose to design a new kind of multifunctional biomaterial, composed of bioactive glass and iron oxide nanoparticles to combine the benefits of bone regeneration and destruction of cancerous cells through magnetic hyperthermia. Indeed, these particles could be implanted into the cavity originating from the tumor removal, and the heat produced by the magnetic particles in an alternative magnetic field would destroy selectively the remaining or resurgent cancerous cells. Finally, the bioactive glass would induce the bone regeneration in the cavity. In a first part of this work, the influence of the synthesis parameters (sol-gel process) on the composition and the textural properties of bioactive nanoparticles (SiO2-CaO) have been studied. The impact of their composition on their bioactivity has then been investigated. In a second part, core/shell nanoparticles composed of maghemite (γ-Fe2O3) and bioactive glass (SiO2-CaO) have been synthesized and characterized. The good performances in terms of heating power (SAR) and bioactivity of the γ-Fe2O3@SiO2-CaO heterostructures pave the way to their use for bone cancer treatment

Elaboration de nanoparticules cœur-coquille magnétiques et bioactives pour le traitement du cancer et la régénération des tissus osseux

International audienc

Nanoparticules de verre bioactif pour la régénération des tissus osseux

National audienc

Deeper Insights into a Bioactive Glass Nanoparticle Synthesis Protocol To Control Its Morphology, Dispersibility, and Composition

International audienc

Unravelling the Impact of Calcium Content on the Bioactivity of Sol–Gel-Derived Bioactive Glass Nanoparticles

International audienceSol-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 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 ratio and 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 which 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 non-cytotoxicity. Hence, biomedical applications can be intended for this sample

Encapsulation of Microperoxidase‐8 into MIL‐101(Cr/Fe) Nanoparticles: A New Biocatalyst for the Epoxidation of Styrene

International audienc

A spin crossover porous hybrid architecture for potential sensing applications

International audienc

Elaboration of Superparamagnetic and Bioactive Multicore–Shell Nanoparticles (γ-Fe 2 O 3 @SiO 2 -CaO): A Promising Material for Bone Cancer Treatment

International audienceThe 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-Fe2O3iron oxide as the core in order to combine the benefits of bone repair thanks to the glass bioactivity and of cancer cells destruction through magnetic hyperthermia (MH). 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 vitrobioactivity assessment performed in SBF (Simulated Body Fluid) showed that these heterostructures exhibit a good heating capacity and a fast mineralization process (hydroxyapatite forming ability). In addition, their in vitrocytocompatibility, evaluated in the presence of Human Mesenchymal Stem Cells (h-MSCs) during 3 and 7 days, has been demonstrated. These firstfindings suggest that γ-Fe2O3@SiO2-CaO heterostructures are a promising biomaterial to fill bone defects resulting from bone tumors resection, as they have the ability to both repair bone tissue and to act as thermo-seeds for cancer therap

Magnetic bioactive glass nano-heterostructures: a deeper insight into magnetic hyperthermia properties in the scope of bone cancer treatment

International audiencePrimary 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