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The synthesis of magnetic nanoparticles (based on iron oxide or Zn/Mn ferrite) has been optimized, through the evaluation of different parameters, for encapsulation into human and murine red blood cells.

The growing interest in multifunctional nano-objects based on polymers and magnetic nanoparticles for biomedical applications motivated us to develop a scale-up protocol to increase the yield of polymeric magnetic nanobeads while aiming at keeping the structural features at optimal conditions. The protocol was applied to two different types of magnetic ferrite nanoparticles: the Mn-ferrite selected for their properties as contrast agents in magnetic resonance imaging and iron oxide nanostar shaped nanoparticles chosen for their heat performance in magnetic hyperthermia. At the same time, some experiments on surface functionalization of nanobeads with amino modified polyethyelene glycol (PEG) molecules have provided further insight into the formation mechanism of magnetic nanobeads and the need to cross-link the polymer shell to improve the stability of the beads, making them more suitable for further manipulation and use. The present work summarizes the most important parameters required to be controlled for the upscaling of nanobead synthesis in a bench protocol and proposes an alternative cross-linking strategy based on prefunctionalization of the polymer prior to the nanobead formation as a key parameter to improve the nanobead structural stability in solutions at different pHs and during surface functionalization.

Versatile methods are here presented for the assembling of magnetic nanoparticles in controlled super-structures with different final aspect ratios. The first step of the procedure is based on the destabilization, and consequently clustering, of a dextran-coated nanoparticles suspension, altering the colloidal stability of the initial building blocks. Subsequently, a second polysaccharide shell, based on chitosan, is grafted to the super-structure surface, for stopping the aggregation of the nanoparticles and enhancing the stability of the resulting assembly. For achieving a finer control of the process, spherical magnetic clusters (SMC) are prepared through a microfluidic aided clustering, investigating the contribution of flow rates and injection scheme geometry to the nanoparticle assembly. Besides, the use of static magnetic fields applied during the first step results in the preparation of micrometric elongated magnetic super-structures (EMS), tuning the average aspect ratio up to a value of 13±4.

A novel biotechnological approach to the preparation of Ir-doped luminescent silica-based nanostructures is proposed availing use of diatoms microalgae which generate highly nanostructured biosilica shells (frustules) by in vivo biomineralization of orthosilicic acid. After the in vivo incorporation of a phosphorescent organometallic complex (Ir-1) in Thalassiosira weissflogii diatom frustules (DFs), bulk functionalized phosphorescent silica-based nanostructures are obtained by isolation and proper ultrafine processing of Ir-1-doped DFs. High-resolution characterization reveals the presence of phosphorescent hybrid organic/inorganic clusters composed of biogenic silica NPs intimately trapped within the diatom organic residual matter. The biofactory strategy investigated herein can be a sustainable, cost-effective, and scalable route to transition metal-doped silica nanomaterials and can pave the way to a great variety of heavy-metal and rare-earth metal doped silica nanostructures, whose applications range from photonics to imaging, sensing, and biomedicine.

Miniaturized optical diagnostics might be greatly favored by the availability of effective, conformable UV light sources combining reduced size with mechanical flexibility. Here we report on our recent results on ZnO-incorporated nanofibers, exhibiting optical gain and polarized emission, used to obtain flexible UV lasers operating at room-temperature. The research leading to these results has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 682157, “xPRINT”), from the Italian Minister of University and Research (PRIN 2017PHRM8X) and from the University of Pisa (PRA “ANISE”).

Ubiquitous in nature, polyamines (PAs) are a class of low-molecular aliphatic amines critically involved in cell growth, survival and differentiation. The polycation behavior is validated as a successful strategy in delivery systems to enhance oligonucleotide loading and cellular uptake. In this study, the chemical features and the functional roles of the PA spermidine are synergistically exploited in the synthesis and bioactive functionalization of SiO2-based structures. Inspired by biosilicification, the role of spermidine is assessed both as catalyst and template in a biomimetic one-pot synthesis of dense silica-based particles (SPs) and as a competitive agent in an interfacial reassembly strategy, to empty out SPs and generate spermidine-decorated hollow silica nanoporous pods (spd-SNPs). Spermidine bioactivity is then employed for targeting tumor cell over-expressed polyamine transport system (PTS) and for effective delivery of functional miRNA into melanoma cells. Spermidine decoration promotes spd-SNP cell internalization mediated by PTS and along with hollow structure enhances oligonucleotide loading. Accordingly, the functional delivery of the tumor suppressor miR-34a 3p resulted in intracellular accumulation of histone-complexed DNA fragments associated with apoptosis. Overall, the results highlight the potential of spd-SNP as a multi-agent anticancer therapy.

The miniaturization of diagnostic devices that exploit optical detection schemes requires the design of light-sources combining small size, high performance for effective excitation of chromophores, and mechanical flexibility for easy coupling to components with complex and non-planar shapes. Here, ZnO nanowire-in-fiber hybrids with internal architectural order are introduced, exhibiting a combination of polarized stimulated emission, low propagation losses of light modes, and structural flexibility. Ultrafast transient absorption experiments on the electrospun material show optical gain which gives rise to amplified spontaneous emission, with threshold lower than the value found in films. These systems are highly flexible and can conveniently conform to curved surfaces, which makes them appealing active elements for various device platforms, such as bendable lasers, optical networks and sensors, as well as for application in bioimaging, photo-crosslinking, and optogenetics., 50 pages, 17 figures, 1 table, ACS Nano, 2020

In the field of nanomedicine, superparamagnetic nanoparticles are one of the most studied nanomaterials for theranostics. In this study, a one-pot synthesis of magnetic nanoparticles is presented, with an increased control on particle size from 10 to 40 nm. Monitoring of vacuum level is introduced here as a crucial parameter for achieving a fine particle morphology. The magnetic properties of these nanoparticles are highly affected by disorders or mismatches in crystal structure. A prolonged oxidation step is applied to the obtained nanoparticles to transform the magnetic phases into a pure maghemite one, confirmed by high-resolution X-ray photoelectron spectroscopy analysis, by Mössbauer spectrometry and, indirectly, by increased performances in magnetization curves and in relaxation times. Afterward, the attained nanoparticles are transferred into water by a nonderivatized dextran coating. Thermogravimetric analysis confirms that polysaccharide molecules replace oleic acid on the surface by stabilizing the particles in the aqueous phase and culture media. Preliminary in vitro test reveals that the dextran-coated nanoparticles are not passively internalized from the cells. As a proof of concept, a secondary layer of chitosan assures a positive charge to the nanoparticle surface, thus enhancing cellular internalization.

Inorganic nanoparticles have great potential for application in many fields, including nanomedicine. Within this class of materials, inorganic nanoheterostructures (NHS) look particularly promising as they can be formulated as the combination of different domains; this can lead to nanosystems with different functional properties, which, therefore, can perform different functions at the same time. This review reports on the latest development in the synthesis of advanced NHS for biomedicine and on the tests of their functional properties in in vivo studies. The literature discussed here focuses on the diagnostic and therapeutic applications with special emphasis on cancer. Considering the diagnostics, a description of the NHS for cancer imaging and multimodal imaging is reported; more specifically, NHS for magnetic resonance, computed tomography and luminescence imaging are considered. As for the therapeutics, NHS employed in magnetic hyperthermia or photothermal therapies are reported. Examples of NHS for cancer theranostics are also presented, emphasizing their dual usability in vivo, as imaging and therapeutic tools. Overall, NHS show a great potential for biomedicine application; further studies, however, are necessary regarding the safety associated to their use.

One of the major challenges of drug delivery is the development of suitable carriers for therapeutic molecules. In this work, a novel nanoformulation based on superparamagnetic nanoclusters [magnetic nanocrystal clusters (MNCs)] is presented. In order to control the size of the nanoclusters and the density of magnetic cores, several parameters were evaluated and tuned. Then, MNCs were functionalized with a polydopamine layer (MNC@PDO) to improve their stability in aqueous solution, to increase density of functional groups and to obtain a nanosystem suitable for drug-controlled release. Finally, cisplatin was grafted on the surface of MNC@PDO to exploit the system as a magnetic field-guided anticancer delivery system. The biocompatibility of MNC@PDO and the cytotoxic effects of MNC@PDO-cisplatin complex were determined against human cervical cancer (HeLa) and human breast adenocarcinoma (MCF-7) cells. In vitro studies demonstrated that the MNC@PDO-cisplatin complexes inhibited the cellular proliferation by a dose-dependent effect. Therefore, by applying an external magnetic field, the released drug exerted its effect on a specific target area. In summary, the MNC@PDO nanosystem has a great potential to be used in targeted nanomedicine for the delivery of other drugs or biofunctional molecules.

Molybdenum disulfide (MoS2) has been attracting extraordinary attention for its intriguing optical, electronic and mechanical properties. Here we demonstrate hybrid, organic-inorganic light-emitting nanofibers based on MoS2 nanoparticle dopants obtained through a simple and inexpensive sonication process in N-methyl-2-pyrrolidone and successfully encapsulated in polymer filaments. Defectiveness is found to be kept low, and stoichiometry preserved, by the implemented, gentle exfoliation method that allows the MoS2 nanoparticles to be produced. So-achieved hybrid fibers are smooth, uniform, flawless, and exhibit bright and continuous light emission. Moreover, they show significant capability of waveguiding self-emitted light along their longitudinal axis. These findings suggest the use of emissive MoS2 fibers enabled by gentle exfoliation methods as novel and highly promising optical material for building sensing surfaces and as components of photonic circuits., 22 pages, 9 figures, Nanoscale, 2018

MoS2 nanoparticles are obtained through a highly gentle exfoliation method and are embedded in polymer nanofibers to make them light-emitting., Molybdenum disulfide (MoS2) has been attracting extraordinary attention for its intriguing optical, electronic and mechanical properties. Here, we demonstrate hybrid, organic–inorganic light-emitting nanofibers based on MoS2 nanoparticle dopants obtained through a simple and inexpensive sonication process in N-methyl-2-pyrrolidone and successfully encapsulate the nanofibers in polymer filaments. The gentle exfoliation method used to produce the MoS2 nanoparticles results in low defectiveness and preserves the stoichiometry. The fabricated hybrid fibers are smooth, uniform and flawless and exhibit bright and continuous light emission. Moreover, the fibers show significant capability for waveguiding self-emitted light along their longitudinal axes. These findings suggest that emissive MoS2 fibers formed by gentle exfoliation are novel and highly promising optical materials for sensing surfaces and photonic circuits.

Magnetic hyperthermia (MHT) and photothermal therapy (PTT) are emergent state‐of‐the‐art modalities for thermal treatment of cancer. While their mechanisms of action have distinct physical bases, both approaches rely on nanoparticle‐mediated remote onset of thermotherapy. Yet, are the two heating techniques interchangeable? Here, the heating obtained either with MHT or with PTT is compared. The heating is assessed in distinct environments and involves a set of nanomaterials differing in shape (spheres, cubes, stars, shells, and rods) as well as in composition (maghemite, magnetite, cobalt ferrite, and gold). The nanoparticle's heating efficacy in an aqueous medium is first evaluated. Subsequently, the heating efficiency within the cellular environment, where intracellular processing markedly decreases MHT, is compared. Conversely, endosomal sequestration could have a positive effect on PTT. Finally, iron oxide nanocubes and gold nanostars are compared in MHT and PTT in vivo within the heterogeneous intratumoral environment. Overall, two distinct therapeutic approaches, related to high dosage allowing MHT and low dosage associated with PTT, are identified. It is also demonstrated that PTT mediated by magnetic nanoparticles has an efficacy that is comparable to that of plasmonic nanoparticles, but only at significant nanoparticle dosages. At low concentrations, only plasmonic nanoparticles can deliver a therapeutic heating.

Alginate (ALG) and chitosan (CS) have been extensively used for biomedical applications; however, data relative to immune responses exerted by them are scarce. We synthesized a submicron vesicle system (SV) displaying a CS shell over an ALG core. Intravenous injection of these promising carriers could be a possible route of delivery; therefore, we evaluated their impact on human peripheral blood mononuclear cells (PBMCs). By this ex vivo approach, we established how SV chemical physical Alainate characteristics affected the immune cells in terms of cellular uptake, viability, and state of activation. By flow cytometry, we demonstrated that SVs were internalized by PBMCs with differential trends. No substantial necrotic and apoptotic signals were recorded, and SVs weakly affected activation status of PBMCs (concerning the markers CD69, CD25, CD80, and the cytokines TNF-alpha and IL-6), showing high immune biocompatibility and low immunomodulating properties. Our findings gain particular value toward the biomedical applications of SVs and make these polymer-based structures more attractive for translation into clinical uses.

International audience; In order to give insights into how anisotropic nano-objects interact with living cell membranes, and possibly self-assemble, we designed magnetic nanorods with average size around 100 nm x 1µm by assembling iron oxide nanocubes within a polymeric matrix under a magnetic field. We then explored the nano-bio interface at the cell membrane under the influence of a rotating magnetic field. We observed a complex structuration of the nanorods intertwined with the membranes. Unexpectedly, after a magnetic rotating stimulation, the resulting macrorods were able to rotate freely for multiple rotations, revealing the creation of a bio-magnetic torsion pendulum.

TGFβ1 pathway antagonists have been considered promising therapies to attenuate TGFβ downstream signals in cancer cells. Inhibiting peptides, as P-17 in this study, are bound to either TGFβ1 or its receptors, blocking signal transduction. However, for efficient use of these TGFβ1antagonist as target therapeutic tools, improvement in their delivery is required. Here, a plasmid carrying specific shDNA (SHT-DNA), small interfering RNA (siRNA), and the peptide (P-17) were loaded separately into folic acid (FA)-functionalized nano-carriers made of Bovine Serum Albumin (BSA). The two building blocks of the carrier, (BSA and FA) were used because of the high affinity of albumin for liver and for the overexpression of folate receptors on the membrane of hepatocellular carcinoma cells. The empty and the encapsulated carriers were thoroughly investigated to characterize their structure, to evaluate the colloidal stability and the surface functionalization. The entrapment of SHT-DNA, siRNA and P-17, respectively, was demonstrated by morphological and quantitative analysis. Finally, cellular studies were performed to assess the targeting efficiency of the hybrid carriers. These vectors were used because of the high affinity of albumin for liver and for the overexpression of folate receptors on the membrane hepatocellular carcinoma cells. The empty and the encapsulated carriers were thoroughly investigated to characterize their structure, to evaluate the colloidal stability and the surface functionalization. The entrapment of SHT-DNA, siRNA and P-17, respectively, was demonstrated by morphological and quantitative analysis. Graphical Abstract: A novel fabrication of Hybrid Polymeric-Protein Nano-Carriers (HPPNC) for delivering TGF β1 inhibitors to HCC cells has been developed. SHT-DNA, siRNA and P-17 have been successfully encapsulated. TGF β1 inhibitors-loaded HPPNC were efficiently uptaken by HLF cells. [InlineMediaObject not available: see fulltext.].

Aim of this work was to investigate whether a surface coating with poly(ethylene glycol) (PEG) makes halloysite clay nanotubes (HNTs) biocompatible up to a concentration level suitable for their effective employment as ultrasound contrast agents. Such a concentration level has been recently identified in a contrast dose of 1.50 mg/mL., which has been shown to be particularly suitable for automatic HNT detection within echographic images acquired through a clinically-available ultrasound device employing conventional diagnostic settings. The dose- and time-dependent cytotoxicity of uncoated and PEG-coated HNTs was evaluated in vitro by MTT cell viability assay carried out on two different human cell lines: SKOV-3 (human ovarian carcinoma cells) and MG-63 (human osteosarcoma cells). Cells were each time incubated for 6 to 72 h in the presence of HNTs at a concentration ranging from 0.25 to 1.5 mg/mL before the MTT test was performed. Obtained results showed that, for both the considered cell lines., viability was substantially unaffected for any tested combination of incubation time and PEG-coated HNT concentration. On the other hand., when the cells were incubated with uncoated HNTs significant reductions in viability (indicative of cytotoxic effects) were visible after a 48-h incubation for each adopted nanoparticle dose. On these bases., PEG coating can be considered a highly effective method to improve the biocompatibility of HNTs., which in turn has a very strong potential for an effective employment as ultrasound contrast and drug delivery agent.

The pursuit of innovative, multifunctional, more efficient, and safer treatments is a major challenge in preclinical nanoparticle-mediated thermotherapeutic research. Here, we report that iron oxide nanoparticles have the dual capacity to act as both magnetic and photothermal agents. We further explore every key aspect of this magnetophotothermal approach, choosing iron oxide nanocubes for their high efficiency for the magnetic hyperthermia modality itself. In aqueous suspension, the nanocubes' exposure to both: an alternating magnetic field and near-infrared laser irradiation (808 nm), defined as the DUAL-mode, amplifies the heating effect 2- to 5-fold by comparison with magnetic stimulation alone, yielding unprecedented heating powers (specific loss powers) up to 5000 W/g. In cancer cells, the laser excitation restores the optimal efficiency of magnetic hyperthermia, otherwise inhibited by intracellular confinement, resulting in a remarkable heating efficiency in the DUAL-mode (up to 15-fold amplification), with respect to the magnetophotothermal mode. As a consequence, the dual action yielded complete apoptosis-mediated cell death. In solid tumors in vivo, single-mode treatments (magnetic or laser hyperthermia) reduced tumor growth, while DUAL-mode treatment resulted in complete tumor regression, mediated by heat-induced tumoral cell apoptosis and massive denaturation of the collagen fibers, and a long-lasting thermal efficiency over repeated treatments.

A versatile method for decorating magnetic nanobeads (being composite materials from polymers and superparamagnetic nanoparticles) with silver nanoparticles of 3-6 nm size is presented. Control over the silver nanoparticle coverage at the nanobead surface is achieved by changing the reaction parameters. Moreover, the silver-decorated magnetic nanobeads (Ag-MNBs) are studied with respect to their in vitro cytotoxicity on two distinct tumour cell lineages under different parameters, i.e., dose, incubation time, magnetic field applied during the culturing, silver ion leakage, and colloidal stability. It is found that enhanced magnetically mediated cellular uptake and silver ion leakage from the Ag-MNBs surface are the main factors which affect the toxicity of the Ag-MNBs and allow the half-maximal inhibitory dose of silver to be reduced to only 32 μg mL(-1) . Furthermore, a synergic cytotoxicity induced by photo-activation of silver nanoparticles was also found.

We present a simple and cost-effective method for rendering networks of cellulose fibers, such as paper, fabrics or membranes, superparamagnetic by impregnating the individual fibers with a reactive acrylic monomer. The cellulose fibers are wetted by a cyanoacrylate monomer solution containing superparamagnetic manganese ferrite colloidal nanoparticles. Upon moisture initiated polymerization of the monomer on the fiber surfaces, a thin nanocomposite shell forms around each fiber. The nanocomposite coating renders the cellulose fibers water repellent and magnetically responsive. Magnetic and microscopy studies prove that the amount of the entrapped nanoparticles in the nanocomposite shell is fully controllable, and that the magnetic response is directly proportional to this amount. A broad range of applications can be envisioned for waterproof magnetic cellulose materials (such as magnetic paper/tissues) obtained by such a simple yet highly efficient method.

Aim: Most of the research efforts in magnetic targeting have been focused on the development of magnetic nanovectors, while the investigation of methods for tracking their magnetic targeting efficiency remains inappropriately addressed. We propose herein a miniaturized approach for appraising magnetophoretic mobility at the nanoscale. Materials & methods: A simple and easy-to-use chamber including a microtip as a magnetic attractor was developed to perform magnetophoretic measurement at the size scale of nano-objects, and under bright field or fluorescence microscopy. Different sets of magnetic nanocontainers were produced and their magnetophoretic mobility was investigated. Real-time observations of the Brownian motion of the nanocontainers were also carried out for simultaneous size determination. Results: Attraction of the nanocontainers at the microtip is demonstrated as a qualitative method that immediately distinguishes magnetically responsive nano-objects. The combination of the analysis of Brownian motion, together with the magnetophoretic mobility, inferred both the size, the magnetophoretic velocity and the magnetic content of the nanocontainers. Additionally, nanomagnetophoresis experiments under fluorescence microscopy provided information on the constitutive core/shell integrity of the nanocontainers and the co-internalization of a fluorescent cargo. Conclusion: This nanomagnetophoresis method represents a promising tool to estimate the feasibility of magnetic targeting in laboratory routine. Original submitted 28 November 2011; Revised submitted 28 February 2012; Published online 18 June 2012

Superparamagnetic nanocarriers with tunable pH dependence of the surface charge are designed by a simple co-precipitation method. By exploiting electrostatic interactions, cationic or anionic payloads can be adsorbed and desorbed depending on the pH. On three different resulting nanocarrier systems, experiments of loading and release of gold nanoparticles as well as effective siRNA loading and in vitro delivery on human cells are performed.

We demonstrate a simple but highly efficient technique to introduce multifunctional properties to cellulose fiber networks by wetting them with ethyl-cyanoacrylate monomer solutions containing various suspended organic submicrometer particles or inorganic nanoparticles. Solutions can be applied on cellulosic surfaces by simple solution casting techniques or by dip coating, both being suitable for large area applications. Immediately after solvent evaporation, ethyl-cyanoacrylate starts cross-linking around cellulose fibers under ambient conditions because of naturally occurring surface hydroxyl groups and adsorbed moisture, encapsulating them with a hydrophobic polymer shell. Furthermore, by dispersing various functional particles in the monomer solutions, hydrophobic ethyl-cyanoacrylate nanocomposites with desired functionalities can be formed around the cellulose fibers. To exhibit the versatility of the method, cellulose sheets were functionalized with different ethyl-cyanoacrylate nanocomposite shells comprising submicrometer wax or polytetrafluoroethylene particles for superhydophobicity, MnFe 2O 4 nanoparticles for magnetic activity, CdSe/ZnS quantum dots for light emission, and silver nanoparticles for antimicrobial activity. Morphological and functional properties of each system have been studied by scanning and transmission electron microscopy, detailed contact angle measurements, light emission spectra and E. coli bacterial growth measurements. A plethora of potential applications can be envisioned for this technique, such as food and industrial packaging, document protection, catalytic cellulosic membranes, textronic (electrofunctional textiles), electromagnetic devices, authentication of valuable documents, and antimicrobial wound healing products to name a few. © 2011 American Chemical Society.

Medical nanoplatforms based on clusters of superparamagnetic nanoparticles decorated with a PNIPAM thermo-responsive shell have been synthesized and used as drug carriers for doxorubicin (DOXO), a common chemotherapeutic agent. The nanosystem here developed has a total diameter below 200 nm and exploits the temperature responsive behaviour of the PNIPAM polymeric shell for the controlled loading and release of DOXO. The system has been tested in vitro on tumour cells and it clearly demonstrates the effectiveness of drug polymer encapsulation and time-dependent cell death induced by the doxorubicin release. Comparative cellular studies of the DOXO loaded nanoplatform in the presence or absence of an external magnet (0.3 T) showed the synergic effect of accumulation and enhanced toxicity of the system, when magnetically guided, resulting in the enhanced efficacy of the system.

Smart materials able to sense environmental stimuli can be exploited as intelligent carrier systems. Acidic pH-responsive polymers, for instance, exhibit a variation in the ionization state upon lowering the pH, which leads to their swelling. The different permeability of these polymers as a function of the pH could be exploited for the incorporation and subsequent release of previously trapped payload molecules/nanoparticles. We provide here a proof of concept of a novel use of pH-responsive polymer nanostructures based on 2-vinylpyridine and divinylbenzene, having an overall size below 200 nm, as cargo system for magnetic nanoparticles, for oligonucleotide sequences, as well as for their simultaneous loading and controlled release mediated by the pH.

Nanostructures displaying fluorescence and magnetic properties at the same time are potentially useful for achieving simultaneous bio-separation and bio-sensing (e.g., magnetic separation coupled with multiplexing optical detection of different tumour cell populations). Spherical nanobeads that display both fluorescent and magnetic features are reported; they are fabricated by grafting fluorescent oligothiophene molecules to an amphiphilic polymer that is then used to enwrap iron oxide nanoparticles, which acts as the magnetic domain. By tuning experimental conditions, control over the number of magnetic nanoparticles per bead and over the bead diameter (30-400 nm) was achieved. A cell separation efficiency of the level required for cell sorting applications is also reported.

The ongoing nanotech revolution has the potential to transform diagnostic and therapeutic methods. Stimuli-triggered nanotherapies based on remotely activated agents have become attractive alternatives to conventional chemotherapy. Herein, we designed an optimized smart nanoplatform based on dually loaded hybrid liposomes to achieve enhanced tumor therapy. The aqueous core was highly loaded with iron oxide nanoparticles, while the lipid bilayer was supplied with a photosensitizer payload. The double cargo translated into double functionality: generation of singlet oxygen under laser excitation and heat production under alternating magnetic field stimulation, coupling photodynamic therapy (PDT) to magnetic hyperthermia (MHT). These liposomes address both therapeutic agents within tumor cells, and the combined PDT/MHT therapy resulted in complete cancer cell death in vitro while total solid-tumor ablation was achieved in an in vivo rodent model.

Iron oxide nanocubes (IONCs) represent one of the most promising iron-based nanoparticles for both magnetic resonance image (MRI) and magnetically mediated hyperthermia (MMH). Here, we have set a protocol to control the aggregation of magnetically interacting IONCs within a polymeric matrix in a so-called magnetic nanobead (MNB) having mesoscale size (200 nm). By the comparison with individual coated nanocubes, we elucidate the effect of the aggregation on the specific adsorption rates (SAR) and on the T-1 and T-2 relaxation times. We found that while SAR values decrease as IONCs are aggregated into MNBs but still keeping significant SAR values (200 W/g at 300 kHz), relaxation times show very interesting properties with outstanding values of r(2)/r(1) ratio for the MNBs with respect to single IONCs.

International audience; Magnetic hyperthermia mediated by magnetic nanomaterials is one promising antitumoral nanotherapy, particularly for its ability to remotely destroy deep tumors. More and more new nanomaterials are being developed for this purpose, with improved heat-generating properties in solution. However, although the ultimate target of these treatments is the tumor cell, the heating efficiency, and the underlying mechanisms, are rarely studied in the cellular environment. Here we attempt to fill this gap by making systematic measurements of both hyperthermia and magnetism in controlled cell environments, using a wide range of nanomaterials. In particular, we report a systematic fall in the heating efficiency for nanomaterials associated with tumour cells. Real-time measurements showed that this loss of heat-generating power occurred very rapidly, within a matter of minutes. The fall in heating correlated with the magnetic characterization of the samples, demonstrating a complete inhibition of the Brownian relaxation in cellular conditions.

International audience; Recent advances in cell therapy and tissue engineering opened new windows for regenerative medicine, but still necessitate innovative noninvasive imaging technologies. We demonstrate that high-resolution magnetic resonance imaging (MRI) allows combining cellular-scale resolution with the ability to detect two cell types simultaneously at any tissue depth. Two contrast agents, based on iron oxide and gadolinium oxide rigid nanoplatforms, were used to "tattoo" endothelial cells and stem cells, respectively, with no impact on cell functions, including their capacity for differentiation. The labeled cells' contrast properties were optimized for simultaneous MRI detection: endothelial cells and stem cells seeded together in a polysaccharide-based scaffold material for tissue engineering appeared respectively in black and white and could be tracked, at the cellular level, both in vitro and in vivo. In addition, endothelial cells labeled with iron oxide nanoparticles could be remotely manipulated by applying a magnetic field, allowing the creation of vessel substitutes with in-depth detection of individual cellular components.

Magnetic liposomes offer opportunities as theranostic systems. The prerequisite for efficient imaging, tissue targeting or hyperthermia is high magnetic load of these vesicles. Here we describe the preparation of Ultra Magnetic Liposomes (UMLs), which may encapsulate iron oxide nanoparticles in a volume fraction of up to 30%. This remarkable magnetic charge provides UMLs with high magnetic mobilities, MRI relaxivities, and heating capacities for magnetic hyperthermia. Moreover, these UMLs are rapidly and efficiently internalized by cultured tumor cells and, when they are administered to mice, they can be vectorized to tumors by an external magnet.

We report on the fabrication and single electron tunneling behaviour of large scale arrays of nanogap electrodes bridged by bisferrocene-gold nanoparticle hybrids (BFc-AuNP). Coulomb staircase was observed in the low temperature current-voltage curves measured on the junctions with asymmetric tunnel barriers. On the other hand, junctions with symmetric tunneling barrier exhibited mere nonlinear current voltage characteristics without discrete staircase. The experimental results agreed well with simulations based on the orthodox theory. The junction resistance showed thermally activated conduction behaviour at higher temperature. The overall voltage and temperature dependent results show that the transport behaviour of the large arrays of single particle devices obtained by a facile optical lithography and chemical etching process corresponds with the behaviour of single particle devices fabricated by other techniques like e-beam lithography and mechanical breaking methods.

Iron oxide nanocrystals (IONCs) are appealing heat mediator nanoprobes in magnetic-mediated hyperthermia for cancer treatment. Here, specific absorption rate (SAR) values are reported for cube-shaped water-soluble IONCs prepared by a one-pot synthesis approach in a size range between 13 and 40 nm. The SAR values were determined as a function of frequency and magnetic field applied, also spanning technical conditions which are considered biomedically safe for patients. Among the different sizes tested, IONCs with an average diameter of 19 ± 3 nm had significant SAR values in clinical conditions and reached SAR values up to 2452 W/g(Fe) at 520 kHz and 29 kAm(-1), which is one of the highest values so far reported for IONCs. In vitro trials carried out on KB cancer cells treated with IONCs of 19 nm have shown efficient hyperthermia performance, with cell mortality of about 50% recorded when an equilibrium temperature of 43 °C was reached after 1 h of treatment.

Trifunctional polymer nanobeads are prepared by destabilization of a mixture of magnetic nanoparticles, quantum dots, and an amphiphilic polymer, followed by functionalization of the bead surface with folic acid molecules. The distribution of the nanoparticles within the nanobeads can be tuned using either acetonitrile or water as destabilizing solvent. The luminescence of the resulting beads can be tuned by varying the ratio of quantum dots per magnetic nanoparticles. The application of an external magnetic field (such as a small static magnet of 0.3 T) to the magnetic-fluorescent nanobeads allows the quantitative accumulation of the beads within a few hours depending on the total size of the beads. Furthermore, specific targeting of cancer cells overexpressing folate receptors is achieved thanks to the folic acid decorating the surface of the as-synthesized nanobeads. Folate receptor mediated cellular uptake of the folic acid-functionalized nanobeads is proven via both confocal imaging and transmission electron microscopy characterization. Cell sorting experiments performed with trifunctional nanobeads show quantitative recovering of targeted cells even when they are present at low percentage (up to 1%).

In the last decade the progress achieved on the synthesis of inorganic nanostructures has been accompanied by the parallel exploitation of these systems in various fields, among them are biology and medicine. We provide here an overview of the iron-based inorganic nanostructured materials that have been developed and tested in these fields. We will highlight the major concepts on the preparation, physical properties and applications of such nanostructures, starting from the most investigated iron oxide nanoparticles. We will describe then the new generation of inorganic hybrid nanostructures, which are structures that integrate in each nano-object multiple inorganic nanocrystals of different materials. In our discussion we will focus on those works that have provided a sound proof of concept on the potential of the various systems as diagnostic and therapeutic agents.

Nanostructures displaying fluorescence and magnetic properties at the same time are potentially useful for achieving simultaneous bio-separation and bio-sensing (e.g., magnetic separation coupled with multiplexing optical detection of different tumour cell populations). Spherical nanobeads that display both fluorescent and magnetic features are reported; they are fabricated by grafting fluorescent oligothiophene molecules to an amphiphilic polymer that is then used to enwrap iron oxide nanoparticles, which acts as the magnetic domain. By tuning experimental conditions, control over the number of magnetic nanoparticles per bead and over the bead diameter (30-400 nm) was achieved. A cell separation efficiency of the level required for cell sorting applications is also reported.

A one-pot, two-step colloidal strategy to prepare bimagnetic hybrid nanocrystals (HNCs), comprising size-tuned fcc FePt and inverse spinel cubic iron oxide domains epitaxially arranged in a heterodimer configuration, is described. The HNCs have been synthesized in a unique surfactant environment by temperature-driven sequential reactions, involving the homogeneous nucleation of FePt seeds and the subsequent heterogeneous growth of iron oxide. This self-regulated mechanism offers high versatility in the control of the geometric features of the resulting heterostructures, circumventing the use of more elaborate seeded growth techniques. It has been found that, as a consequence of the exchange coupling between the two materials, the HNCs exhibit tunable single-phase-like magnetic behavior, distinct from that of their individual components. In addition, the potential of the heterodimers as effective contrast agents for magnetic resonance imaging techniques has been examined.

Poly(maleic anhydride-alt-1-octadecene), a cheap and commercially available polymer, was used to water-solubilize colloidal nanocrystals with various compositions, morphologies, and sizes. Highly pure nanoparticles with homogeneous distributions of sizes and surface charges were obtained after a single purification step of the polymer-coated particles by ultracentrifugation, saving precious time as compared to a previously published and similar polymer coating procedure. This simple strategy proved also to be generally applicable and represents a valid methodology to water-solubilize nanoparticles.

The combination of materials that possess different properties (such as, for instance, fluorescence and magnetism) into one single object of nanoscale size represents an attractive challenge for biotechnology, especially for their potential relevance in biomedical applications. We report here the preparation of novel bifunctional conjugates based on the linkage of inorganic nanoparticles to organic oligothiophene fluorophores (OTFs). In comparison to the organic dyes commonly used in bioimaging and more similarly to colloidal quantum dots, OTFs have broad optical absorption spectra, and therefore OTF fluorophores emitting at different colors can be excited with a single excitation source, allowing for easier multiplexing analysis. In this work we show the preparation of OTF-nanoparticle conjugates based on gold and iron oxide nanoparticles and their characterization using different techniques such as gel electrophoresis, photoluminescence spectroscopy, dynamic light scattering, and so on. In addition, by performing an in vitro study on human tumor cells we show that OTF-nanoparticle conjugates emitting at different colors can be used for multiplexing detection. Also, in the case of iron oxide-OTF conjugates, once uptaken by the cells, we show that they preserve both their fluorescent and their magnetic properties.

International audience; There is a great deal of interest in the development of nanoplatforms gathering versatility and multifunctionality. The strategy reported herein meets these requirements and further integrates a cell-friendly shell in a bio-inspired approach. By taking advantage of a cell mechanism of biomolecule transport using vesicles, we engineered a hybrid biogenic nanoplatform able to encapsulate a set of nanoparticles regardless of their chemistry or shape. As a proof of versatility, different types of hybrid nanovesicles were produced: magnetic, magnetic-metallic and magnetic-fluorescent vesicles, either a single component or multiple components, combining the advantageous properties of each integrant nanoparticle. These nanoparticle-loaded vesicles can be manipulated, monitored by MRI and/or fluorescence imaging methods, while acting as efficient nano-heaters. The resulting assets for targeting, imaging and therapy converge for the outline of a new generation of nanosystems merging versatility and multifunctionality into a bio-camouflaged and bio-inspired approach.

The development of fluorescent biolabels for specific targeting and controlled drug release is of paramount importance in biological applications due to their potential in the generation of novel tools for simultaneous diagnosis and treatment of diseases. Dopamine is a neurotransmitter involved in several neurological diseases, such as Parkinson's disease and attention deficit hyperactivity disorder (ADHD), and the controlled delivery of its agonists already proved to have beneficial effects both in vitro and in vivo. Here, we report the synthesis and multiple functionalization of highly fluorescent CdSe/CdS quantum rods for specific biolabeling and controlled drug release. After being transferred into aqueous media, the nanocrystals were made highly biocompatible through PEG conjugation and covered by a carbohydrate shell, which allowed specific GLUT-1 recognition. Controlled attachment of dopamine through an ester bond also allowed hydrolysis by esterases, yielding a smart nanotool for specific biolabeling and controlled drug release.

The following article appeared in Journal of Applied Physics 110.6 (2011): 064907 and may be found at http://scitation.aip.org/content/aip/journal/jap/110/6/10.1063/1.3638695, Superparamagnetic nanostructures are becoming increasingly important as tools for biological and medical applications. We report the study of the movement of rod-shaped assemblies of superparamagnetic nanocrystals under the action of a rotating magnetic field. The dynamic was characterized by means of light scattering detection at different frequencies and for different values of the intensity of the applied external field. The possibility to correlate the motion to the viscosity of the medium is used to monitor viscosity changes inside the liquid. We propose this technique as a valuable tool to monitor viscosity at microscale for application in biological studies., This work was partially supported by the European project Magnifyco (Contract NMP4-SL-2009-228622).