RESUMO
The design of core-shell nanocomposites composed of an iron oxide core and a silica shell offers promising applications in the nanomedicine field, especially for developing efficient theranostic systems which may be useful for cancer treatments. This review article addresses the different ways to build iron oxide@silica core-shell nanoparticles and it reviews their properties and developments for hyperthermia therapies (magnetically or light-induced), combined with drug delivery and MRI imaging. It also highlights the various challenges encountered, such as the issues associated with in vivo injection in terms of NP-cell interactions or the control of the heat dissipation from the core of the NP to the external environment at the macro or nanoscale.
RESUMO
Proteins are great therapeutic candidates as endogenous biomolecules providing a wide range of applications. However, their delivery suffers from some limitations and specifically designed delivery systems having an efficient protein anchoring and delivery strategy are still needed. In this work, we propose to combine large pore stellate mesoporous silica (STMS) with isobutyramide (IBAM), as a "glue" molecule which has been shown promising for immobilization of various biomacromolecules at silica surface. We address here for the first time the ability of such IBAM-modified NPs to sustainably deliver proteins over a prolonged time. In this work, a quantitative loading study of proteins (serum albumin (HSA), peroxidase (HRP), immunoglobulin (IgG) and polylysine (PLL)) on STMS@IBAM is first presented using three complementary detection techniques to ensure precision and avoid protein quantification issues. The results demonstrated a high loading capacity for HSA and HRP (≥ ca. 350 µg.mg-1) but a moderate one for IgG and PLL. After evaluating the physicochemical properties of the loaded particles and their stability over scaling-up and washings, the ability of STMS@IBAM to release proteins over prolonged time was evaluated in equilibrium (static) and flow mimicking (dynamic) conditions and at different temperatures (25, 37, 45 °C). Results show not only the potential of such "glue" functionalized STMS to release proteins in a sustained way, but also the retention of the biological activity of immobilized and released HRP, used as an enzyme model. Finally, an AFM-force spectroscopy study was conducted to decipher the interactions between IBAM and proteins, showing the involvement of different interactions in the adsorption and release processes.
RESUMO
Molecular magnetic resonance imaging (MRI) holds great promise for diagnosis and therapeutic monitoring in a wide range of diseases. However, the low intrinsic sensitivity of MRI to detect exogenous contrast agents and the lack of biodegradable microprobes have prevented its clinical development. Here, we synthetized a contrast agent for molecular MRI based on a previously unknown mechanism of self-assembly of catechol-coated magnetite nanocrystals into microsized matrix-based particles. The resulting biodegradable microprobes (M3P for microsized matrix-based magnetic particles) carry up to 40,000 times higher amounts of superparamagnetic material than classically used nanoparticles while preserving favorable biocompatibility and excellent water dispersibility. After conjugation to monoclonal antibodies, targeted M3P display high sensitivity and specificity to detect inflammation in vivo in the brain, kidneys, and intestinal mucosa. The high payload of superparamagnetic material, excellent toxicity profile, short circulation half-life, and widespread reactivity of the M3P particles provides a promising platform for clinical translation of immuno-MRI.
RESUMO
The controlled design of robust, well reproducible, and functional nanomaterials made according to simple processes is of key importance to envision future applications. In the field of porous materials, tuning nanoparticle features such as specific area, pore size and morphology by adjusting simple parameters such as pH, temperature or solvent is highly needed. In this work, we address the tunable control of the pore morphology of mesoporous silica (MS) nanoparticles (NPs) with the sol-gel reaction temperature (Tsg). We show that the pore morphology of MS NPs alone or of MS shell covering iron oxide nanoparticles (IO NPs) can be easily tailored with Tsg orienting either towards stellar (ST) morphology (large radial pore of around 10 nm) below 80 °C or towards a worm-like (WL) morphology (small randomly oriented pores channel network, of 3-4 nm pore size) above 80 °C. The relaxometric and magnetothermal features of IO@STMS or IO@WLMS core shell NPs having respectively stellar or worm-like morphologies are compared and discussed to understand the role of the pore structure for MRI and magnetic hyperthermia applications.
Assuntos
Portadores de Fármacos/química , Nanopartículas/química , Dióxido de Silício/química , Concentração de Íons de Hidrogênio , Imageamento por Ressonância Magnética , Nanopartículas/ultraestrutura , Tamanho da Partícula , Porosidade , TemperaturaRESUMO
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.
Assuntos
Antineoplásicos/uso terapêutico , Materiais Biocompatíveis/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Células-Tronco Mesenquimais/efeitos dos fármacos , Nanopartículas/química , Antineoplásicos/química , Materiais Biocompatíveis/química , Compostos de Cálcio/química , Células Cultivadas , Óxido Ferroso-Férrico/química , Humanos , Óxidos/química , Tamanho da Partícula , Dióxido de Silício/química , Propriedades de SuperfícieRESUMO
In this work, we describe the design and the use of a novel theranostic hybrid nanocomposite made of an iron oxide core and a mesoporous silica shell (IO@MS) of ca. 30 nm coated by human serum albumin (HSA) layer for magnetic resonance imaging and drug delivery applications. The porosity of IO@MS nanoparticles was loaded with an antitumoral drug, Doxorubicin (Dox) reaching a high drug loading capacity (DLC) of 34 w%. To entrap the drug, a tight HSA coating held via isobutyramide (IBAM) binders was deposited. We show that this protein nanoassembly entraps the drugs efficiently and behaves as an innovative enzyme-sensitive gatekeeper that is degraded upon protease action. Finally we assess the Dox release in a 3D cell model via confocal imaging and its cytotoxicity is shown by growth inhibition studies on liver cancer cell spheroids.