Grafting of Crown Ether and Cryptand Macrocycles on Large Pore Stellate Mesoporous Silica for Sodium Cation Extraction.

Regulation of the sodium cations level in the case of renal failure diseases is a very challenging task for clinicians, and new pollutant extractors based on nanomaterials are emerging as potential treatments. In this work, we report different strategies for the chemical functionalization of biocompatible large pore mesoporous silica, denoted stellate mesoporous silica (STMS), with chelating ligands able to selectively capture sodium. We address efficient methods to covalently graft highly chelating macrocycles onto STMS NPs such as crown ethers (CE) and cryptands (C221) through complementary carbodiimidation reactions. Regarding sodium capture in water, C221 cryptand-grafted STMS showed better capture efficiency than CE-STMS due to higher sodium atom chelation in the cryptand cage (Na+ coverage of 15.5% vs. 3.7%). The sodium selectivity was hence tested with C221 cryptand-grafted STMS in a multi-element aqueous solution (metallic cations with the same concentration) and in a solution mimicking peritoneal dialysis solution. Results obtained indicate that C221 cryptand-grafted STMS are relevant nanomaterials to extract sodium cations in such media and allow us to regulate their levels.

UV-Accelerated Synthesis of Gold Nanoparticle-Pluronic Nanocomposites for X-ray Computed Tomography Contrast Enhancement.

Eco-friendly chemical methods using FDA-approved Pluronic F127 (PLU) block copolymer have garnered much attention for simultaneously forming and stabilizing Au nanoparticles (AuNPs). Given the remarkable properties of AuNPs for usage in various fields, especially in biomedicine, we performed a systematic study to synthesize AuNP-PLU nanocomposites under optimized conditions using UV irradiation for accelerating the reaction. The use of UV irradiation at 254 nm resulted in several advantages over the control method conducted under ambient light (control). The AuNP-PLU-UV nanocomposite was produced six times faster, lasting 10 min, and exhibited lower size dispersion than the control. A set of experimental techniques was applied to determine the structure and morphology of the produced nanocomposites as affected by the UV irradiation. The MTT assay was conducted to estimate IC50 values of AuNP-PLU-UV in NIH 3T3 mouse embryonic fibroblasts, and the results suggest that the sample is more compatible with cells than control samples. Afterward, in vivo maternal and fetal toxicity assays were performed in rats to evaluate the effect of AuNP-PLU-UV formulation during pregnancy. Under the tested conditions, the treatment was found to be safe for the mother and fetus. As a proof of concept or application, the synthesized Au:PLU were tested as contrast agents with an X-ray computed tomography scan (X-ray CT).

Effect of the Size and Shape of Dendronized Iron Oxide Nanoparticles Bearing a Targeting Ligand on MRI, Magnetic Hyperthermia, and Photothermia Properties-From Suspension to In Vitro Studies.

Functionalized iron oxide nanoparticles (IONPs) are increasingly being designed as a theranostic nanoplatform combining specific targeting, diagnosis by magnetic resonance imaging (MRI), and multimodal therapy by hyperthermia. The effect of the size and the shape of IONPs is of tremendous importance to develop theranostic nanoobjects displaying efficient MRI contrast agents and hyperthermia agent via the combination of magnetic hyperthermia (MH) and/or photothermia (PTT). Another key parameter is that the amount of accumulation of IONPs in cancerous cells is sufficiently high, which often requires the grafting of specific targeting ligands (TLs). Herein, IONPs with nanoplate and nanocube shapes, which are promising to combine magnetic hyperthermia (MH) and photothermia (PTT), were synthesized by the thermal decomposition method and coated with a designed dendron molecule to ensure their biocompatibility and colloidal stability in suspension. Then, the efficiency of these dendronized IONPs as contrast agents (CAs) for MRI and their ability to heat via MH or PTT were investigated. The 22 nm nanospheres and the 19 nm nanocubes presented the most promising theranostic properties (respectively, r2 = 416 s-1·mM-1, SARMH = 580 W·g-1, SARPTT = 800 W·g-1; and r2 = 407 s-1·mM-1, SARMH = 899 W·g-1, SARPTT = 300 W·g-1). MH experiments have proven that the heating power mainly originates from Brownian relaxation and that SAR values can remain high if IONPs are prealigned with a magnet. This raises hope that heating will maintain efficient even in a confined environment, such as in cells or in tumors. Preliminary in vitro MH and PTT experiments have shown the promising effect of the cubic shaped IONPs, even though the experiments should be repeated with an improved set-up. Finally, the grafting of a specific peptide (P22) as a TL for head and neck cancers (HNCs) has shown the positive impact of the TL to enhance IONP accumulation in cells.

Iron Oxide@Mesoporous Silica Core-Shell Nanoparticles as Multimodal Platforms for Magnetic Resonance Imaging, Magnetic Hyperthermia, Near-Infrared Light Photothermia, and Drug Delivery.

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.

Phosphate Capture Enhancement Using Designed Iron Oxide-Based Nanostructures.

Phosphates in high concentrations are harmful pollutants for the environment, and new and cheap solutions are currently needed for phosphate removal from polluted liquid media. Iron oxide nanoparticles show a promising capacity for removing phosphates from polluted media and can be easily separated from polluted media under an external magnetic field. However, they have to display a high surface area allowing high removal pollutant capacity while preserving their magnetic properties. In that context, the reproducible synthesis of magnetic iron oxide raspberry-shaped nanostructures (RSNs) by a modified polyol solvothermal method has been optimized, and the conditions to dope the latter with cobalt, zinc, and aluminum to improve the phosphate adsorption have been determined. These RSNs consist of oriented aggregates of iron oxide nanocrystals, providing a very high saturation magnetization and a superparamagnetic behavior that favor colloidal stability. Finally, the adsorption of phosphates as a function of pH, time, and phosphate concentration has been studied. The undoped and especially aluminum-doped RSNs were demonstrated to be very effective phosphate adsorbents, and they can be extracted from the media by applying a magnet.

Bioconjugation studies of an EGF-R targeting ligand on dendronized iron oxide nanoparticles to target head and neck cancer cells.

A major challenge in nanomedicine is designing nanoplatforms (NPFs) to selectively target abnormal cells to ensure early diagnosis and targeted therapy. Among developed NPFs, iron oxide nanoparticles (IONPs) are good MRI contrast agents and can be used for therapy by hyperthermia and as radio-sensitizing agents. Active targeting is a promising method for selective IONPs accumulation in cancer tissues and is generally performed by using targeting ligands (TL). Here, a TL specific for the epidermal growth factor receptor (EGFR) is bound to the surface of dendronized IONPs to produce nanostructures able to specifically recognize EGFR-positive FaDu and 93-Vu head and neck cancer cell lines. Several parameters were optimized to ensure a high coupling yield and to adequately quantify the amount of TL per nanoparticle. Nanostructures with variable amounts of TL on the surface were produced and evaluated for their potential to specifically target and be thereafter internalized by cells. Compared to the bare NPs, the presence of the TL at the surface was shown to be effective to enhance their internalization and to play a role in the total amount of iron present per cell.

Quantum Advantage in a Molecular Spintronic Engine that Harvests Thermal Fluctuation Energy.

Recent theory and experiments have showcased how to harness quantum mechanics to assemble heat/information engines with efficiencies that surpass the classical Carnot limit. So far, this has required atomic engines that are driven by cumbersome external electromagnetic sources. Here, using molecular spintronics, an implementation that is both electronic and autonomous is proposed. The spintronic quantum engine heuristically deploys several known quantum assets by having a chain of spin qubits formed by the paramagnetic Co center of phthalocyanine (Pc) molecules electronically interact with electron-spin-selecting Fe/C60 interfaces. Density functional calculations reveal that transport fluctuations across the interface can stabilize spin coherence on the Co paramagnetic centers, which host spin flip processes. Across vertical molecular nanodevices, enduring dc current generation, output power above room temperature, two quantum thermodynamical signatures of the engine's processes, and a record 89% spin polarization of current across the Fe/C60 interface are measured. It is crucially this electron spin selection that forces, through demonic feedback and control, charge current to flow against the built-in potential barrier. Further research into spintronic quantum engines, insight into the quantum information processes within spintronic technologies, and retooling the spintronic-based information technology chain, can help accelerate the transition to clean energy.

Protein sustained release from isobutyramide-grafted stellate mesoporous silica nanoparticles.

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.

Tracking the immune response by MRI using biodegradable and ultrasensitive microprobes.

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.

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

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.

A Confinement-Driven Nucleation Mechanism of Metal Oxide Nanoparticles Obtained via Thermal Decomposition in Organic Media.

Thermal decomposition is a very efficient synthesis strategy to obtain nanosized metal oxides with controlled structures and properties. For the iron oxide nanoparticle synthesis, it allows an easy tuning of the nanoparticle's size, shape, and composition, which is often explained by the LaMer theory involving a clear separation between nucleation and growth steps. Here, the events before the nucleation of iron oxide nanocrystals are investigated by combining different complementary in situ characterization techniques. These characterizations are carried out not only on powdered iron stearate precursors but also on a preheated liquid reaction mixture. They reveal a new nucleation mechanism for the thermal decomposition method: instead of a homogeneous nucleation, the nucleation occurs within vesicle-like-nanoreactors confining the reactants. The different steps are: 1) the melting and coalescence of iron stearate particles, leading to "droplet-shaped nanostructures" acting as nanoreactors; 2) the formation of a hitherto unobserved iron stearate crystalline phase within the nucleation temperature range, simultaneously with stearate chains loss and Fe(III) to Fe(II) reduction; 3) the formation of iron oxide nuclei inside the nanoreactors, which are then ejected from them. This mechanism paves the way toward a better mastering of the metal oxide nanoparticles synthesis and the control of their properties.

Unveiling the role of surface, size, shape and defects of iron oxide nanoparticles for theranostic applications.

Iron oxide nanoparticles (IONPs) are well-known contrast agents for MRI for a wide range of sizes and shapes. Their use as theranostic agents requires a better understanding of their magnetic hyperthermia properties and also the design of a biocompatible coating ensuring their stealth and a good biodistribution to allow targeting of specific diseases. Here, biocompatible IONPs of two different shapes (spherical and octopod) were designed and tested in vitro and in vivo to evaluate their abilities as high-end theranostic agents. IONPs featured a dendron coating that was shown to provide anti-fouling properties and a small hydrodynamic size favoring an in vivo circulation of the dendronized IONPs. While dendronized nanospheres of about 22 nm size revealed good combined theranostic properties (r2 = 303 mM s-1, SAR = 395 W gFe-1), octopods with a mean size of 18 nm displayed unprecedented characteristics to simultaneously act as MRI contrast agents and magnetic hyperthermia agents (r2 = 405 mM s-1, SAR = 950 W gFe-1). The extensive structural and magnetic characterization of the two dendronized IONPs reveals clear shape, surface and defect effects explaining their high performance. The octopods seem to induce unusual surface effects evidenced by different characterization techniques while the nanospheres show high internal defects favoring Néel relaxation for magnetic hyperthermia. The study of octopods with different sizes showed that Néel relaxation dominates at sizes below 20 nm while the Brownian one occurs at higher sizes. In vitro experiments demonstrated that the magnetic heating capability of octopods occurs especially at low frequencies. The coupling of a small amount of glucose on dendronized octopods succeeded in internalizing them and showing an effect of MH on tumor growth. All measurements evidenced a particular signature of octopods, which is attributed to higher anisotropy, surface effects and/or magnetic field inhomogeneity induced by tips. This approach aiming at an analysis of the structure-property relationships is important to design efficient theranostic nanoparticles.

Iron Stearate Structures: An Original Tool for Nanoparticles Design.

Iron carboxylates are widely used as iron precursors in the thermal decomposition process or considered as in situ formed intermediate precursors. Their molecular and three-dimensional (3D)-structural nature has been shown to affect the shape, size, and composition of the resulting iron oxide nanoparticles (NPs). Among carboxylate precursors, stearates are particularly attractive because of their higher stability to aging and hydration and they are used as additives in many applications. Despite the huge interest of iron stearates, very few studies aimed up to now at deciphering their full metal-ligand structures and the mechanisms allowing us to achieve in a controlled manner the bottom-up NP formation. In this work, we have thus investigated the molecular structure and composition of two iron stearate precursors, synthesized by introducing either two (FeSt2) or three (FeSt3) stearate (St) chains. Interestingly, both iron stearates consist of lamellar structures with planes of iron polynuclear complexes (polycations) separated with stearate chains in all-trans conformation. The iron content in polycations was found very different between both iron stearates. Their detailed characterizations indicate that FeSt2 is mainly composed of [Fe3-(µ3-O)St6·xH2O]Cl, with no (or few) free stearate, whereas FeSt3 is a mixture of mainly [Fe7(µ3-O(H))6(µ2-OH)xSt12-2x]St with some [Fe3(µ3-O)St6·xH2O]St and free stearic acid. The formation of bigger polynuclear complexes with FeSt3 was related to higher hydrolysis and condensation rates within the iron(III) chloride solution compared to the iron(II) chloride solution. These data suggested a nucleation mechanism based on the condensation of polycation radicals generated by the catalytic departure of two stearate chains from an iron polycation-based molecule.

Small iron oxide nanoparticles as MRI T1 contrast agent: scalable inexpensive water-based synthesis using a flow reactor.

Small iron oxide nanoparticles (IONPs) were synthesised in water via co-precipitation by quenching particle growth after the desired magnetic iron oxide phase formed. This was achieved in a millifluidic multistage flow reactor by precisely timed addition of an acidic solution. IONPs (≤5 nm), a suitable size for positive T1 magnetic resonance imaging (MRI) contrast agents, were obtained and stabilised continuously. This novel flow chemistry approach facilitates a reproducible and scalable production, which is a crucial paradigm shift to utilise IONPs as contrast agents and replace currently used Gd complexes. Acid addition had to be timed carefully, as the inverse spinel structure formed within seconds after initiating the co-precipitation. Late quenching allowed IONPs to grow larger than 5 nm, whereas premature acid addition yielded undesired oxide phases. Use of a flow reactor was not only essential for scalability, but also to synthesise monodisperse and non-agglomerated small IONPs as (i) co-precipitation and acid addition occurred at homogenous environment due to accurate temperature control and rapid mixing and (ii) quenching of particle growth was possible at the optimum time, i.e., a few seconds after initiating co-precipitation. In addition to the timing of growth quenching, the effect of temperature and dextran present during co-precipitation on the final particle size was investigated. This approach differs from small IONP syntheses in batch utilising either growth inhibitors (which likely leads to impurities) or high temperature methods in organic solvents. Furthermore, this continuous synthesis enables the low-cost (<£10 per g) and large-scale production of highly stable small IONPs without the use of toxic reagents. The flow-synthesised small IONPs showed high T1 contrast enhancement, with transversal relaxivity (r2) reduced to 20.5 mM-1 s-1 and longitudinal relaxivity (r1) higher than 10 mM-1 s-1, which is among the highest values reported for water-based IONP synthesis.

Orienting the Pore Morphology of Core-Shell Magnetic Mesoporous Silica with the Sol-Gel Temperature. Influence on MRI and Magnetic Hyperthermia Properties.

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.

Design and applications of protein delivery systems in nanomedicine and tissue engineering.

Proteins are biological macromolecules involved in a wide range of biological functions, which makes them very appealing as therapeutics agents. Indeed, compared to small molecule drugs, their endogenous nature ensures their biocompatibility and biodegradability, they can be used in a large range of applications and present a higher specificity and activity. However, they suffer from unfolding, enzymatic degradation, short half-life and poor membrane permeability. To overcome such drawbacks, the development of protein delivery systems to protect, carry and deliver them in a controlled way have emerged importantly these last years. In this review, the formulation of a wide panel of protein delivery systems either in the form of polymer or inorganic nanoengineered colloids and scaffolds are presented and the protein loading and release mechanisms are addressed. A section is also dedicated to the detection of proteins and the characterization methods of their release. Then, the main protein delivery systems developed these last three years for anticancer, tissue engineering or diabetes applications are presented, as well as the major in vivo models used to test them. The last part of this review aims at presenting the perspectives of the field such as the use of protein-rich material or the sequestration of proteins. This part will also deal with less common applications and gene therapy as an indirect method to deliver protein.

Elaboration of Superparamagnetic and Bioactive Multicore-Shell Nanoparticles (γ-Fe2O3@SiO2-CaO): A Promising Material for Bone Cancer Treatment.

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.

Highly chelating stellate mesoporous silica nanoparticles for specific iron removal from biological media.

In this work, the design of a new generation of functionalized large pore silica nanoparticles is addressed for the specific removal of iron from biological environments. Herein, mesoporous silica with a large pore stellate morphology, denoted STMS, were grafted with the highly specific iron chelating agent desferrioxamine B, DFoB. The challenge of this work was the step by step elaboration of the nanoplatform and the evaluation of its chelating efficiency and selectivity. Hence, the controlled covalent grafting of DFoB specific iron chelator, was successfully achieved ensuring a high grafting rate of chelating ligand of 730 nmol·mg-1 (i.e., 0.85 ligand·nm-2). Furthermore, these highly chelating STMS silica were able to capture iron(III) stabilized with nitrilotriacetic acid (NTA) in solution at physiological pH with a fast kinetics (less than 30 min). For a stoichiometry 0.85:1 (FeNTA : DFoB), the STMS-DFoB nanoparticles allowed reaching capture capacity and efficiency of 480 nmolFe3+/mg SiO2 and 78%, respectively. Regarding the selectivity features of the removal process, studies were performed with two different media composed of various metal ions: (i) an equimolar solution of various metal cations and (ii) a Barth's buffer mimicking the brain solution composition. In both cases, the chelating STMS-DFoB showed a high selectivity for iron versus other ions at the same (Al3+) or different valency (Na+, K+…). Finally, this work paves the way for new nanosystems for metal overload treatments as well as for future highly chelating nanoplatforms that can be used at the interface between depollution and nanomedecine.

Doxorubicin-Loaded Thermoresponsive Superparamagnetic Nanocarriers for Controlled Drug Delivery and Magnetic Hyperthermia Applications.

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.

Wrapped stellate silica nanocomposites as biocompatible luminescent nanoplatforms assessed in vivo.

The engineering of luminescent nanoplatforms for biomedical applications displaying ability for scaling-up, good colloidal stability in aqueous solutions, biocompatibility, and providing an easy detection in vivo by fluorescence methods while offering high potential of functionalities, is currently a challenge. The original strategy proposed here involves the use of large pore (ca. 15 nm) mesoporous silica (MS) nanoparticles (NPs) having a stellate morphology (denoted STMS) on which fluorescent InP/ZnS quantum dots (QDs) are covalently grafted with a high yield (≥90%). These nanoplatforms are after that further coated to avoid a potential QDs release. To protect the QDs from potential release or dissolution, two wrapping methods are developed: (i) a further coating with a silica shell having small pores (≤2 nm) or (ii) a tight polysaccharide shell deposited on the surface of these STMS@QDs particles via an original isobutyramide (IBAM)-mediated method. Both wrapping approaches yield to novel luminescent nanoplatforms displaying a highly controlled structure, a high size monodispersity (ca. 200 and 100 nm respectively) and colloidal stability in aqueous solutions. Among both methods, the IBAM-polysaccharide coating approach is shown the most suitable to ensure QDs protection and to avoid metal cation release over three months. Furthermore, these original STMS@QDs@polysaccharide luminescent nanoplatforms are shown biocompatible in vitro with murine cancer cells and in vivo after injections within zebrafish (ZF) translucent embryos where no sign of toxicity is observed during their development over several days. As assessed by in vivo confocal microscopy imaging, these nanoplatforms are shown to rapidly extravasate from blood circulation to settle in neighboring tissues, ensuring a remanent fluorescent labelling of ZF tissues in vivo. Such fluorescent and hybrid STMS composites are envisioned as novel luminescent nanoplatforms for in vivo fluorescence tracking applications and offer a versatile degree of additional functionalities (drug delivery, incorporation of magnetic/plasmonic core).