Ermanno Miele

Albumin-bound formulation of paclitaxel (Abraxane ABI-007) in the treatment of breast cancer.

Breast cancer is the most common type of malignancy diagnosed in women. In the metastatic setting this disease is still uncurable. Taxanes represent an important class of antitumor agents which have proven to be fundamental in the treatment of advanced and early-stage breast cancer, but the clinical advances of taxanes have been limited by their highly hydrophobic molecular status. To overcome this poor water solubility, lipid-based solvents have been used as a vehicle, and new systemic formulations have been developed, mostly for paclitaxel, which are Cremophor-free and increase the circulation time of the drug. ABI-007 is a novel, albumin-bound, 130-nm particle formulation of paclitaxel, free from any kind of solvent. It has been demonstrated to be superior to an equitoxic dose of standard paclitaxel with a significantly lower incidence of toxicities in a large, international, randomized phase III trial. The availability of new drugs, such as Abraxane®, in association with other traditional and non-traditional drugs (new antineoplastic agents and targeted molecules), will give the oncologist many different effective treatment options for patients in this setting.

Nanoparticle-based delivery of small interfering RNA: challenges for cancer therapy

During recent decades there have been remarkable advances and profound changes in cancer therapy. Many therapeutic strategies learned at the bench, including monoclonal antibodies and small molecule inhibitors, have been used at the bedside, leading to important successes. One of the most important advances in biology has been the discovery that small interfering RNA (siRNA) is able to regulate the expression of genes, by a phenomenon known as RNA interference (RNAi). RNAi is one of the most rapidly growing fields of research in biology and therapeutics. Much research effort has gone into the application of this new discovery in the treatment of various diseases, including cancer. However, even though these molecules may have potential and strong utility, some limitations make their clinical application difficult, including delivery problems, side effects due to off-target actions, disturbance of physiological functions of the cellular machinery involved in gene silencing, and induction of the innate immune response. Many researchers have attempted to overcome these limitations and to improve the safety of potential RNAi-based therapeutics. Nanoparticles, which are nanostructured entities with tunable size, shape, and surface, as well as biological behavior, provide an ideal opportunity to modify current treatment regimens in a substantial way. These nanoparticles could be designed to surmount one or more of the barriers encountered by siRNA. Nanoparticle drug formulations afford the chance to improve drug bioavailability, exploiting superior tissue permeability, payload protection, and the “stealth” features of these entities. The main aims of this review are: to explain the siRNA mechanism with regard to potential applications in siRNA-based cancer therapy; to discuss the possible usefulness of nanoparticle-based delivery of certain molecules for overcoming present therapeutic limitations; to review the ongoing relevant clinical research with its pitfalls and promises; and to evaluate critically future perspectives and challenges in siRNA-based cancer therapy.

3D Hollow Nanostructures as Building Blocks for Multifunctional Plasmonics

We present an advanced and robust technology to realize 3D hollow plasmonic nanostructures which are tunable in size, shape, and layout. The presented architectures offer new and unconventional properties such as the realization of 3D plasmonic hollow nanocavities with high electric field confinement and enhancement, finely structured extinction profiles, and broad band optical absorption. The 3D nature of the devices can overcome intrinsic difficulties related to conventional architectures in a wide range of multidisciplinary applications.

Notch and NF-kB signaling pathways regulate miR-223/FBXW7 axis in T-cell acute lymphoblastic leukemia.

Notch signaling deregulation is linked to the onset of several tumors including T-cell acute lymphoblastic leukemia (T-ALL). Deregulated microRNA (miRNA) expression is also associated with several cancers, including leukemias. However, the transcriptional regulators of miRNAs, as well as the relationships between Notch signaling and miRNA deregulation, are poorly understood. To identify miRNAs regulated by Notch pathway, we performed microarray-based miRNA profiling of several Notch-expressing T-ALL models. Among seven miRNAs, consistently regulated by overexpressing or silencing Notch3, we focused our attention on miR-223, whose putative promoter analysis revealed a conserved RBPjk binding site, which was nested to an NF-kB consensus. Luciferase and chromatin immunoprecipitation assays on the promoter region of miR-223 show that both Notch and NF-kB are novel coregulatory signals of miR-223 expression, being able to activate cooperatively the transcriptional activity of miR-223 promoter. Notably, the Notch-mediated activation of miR-223 represses the tumor suppressor FBXW7 in T-ALL cell lines. Moreover, we observed the inverse correlation of miR-223 and FBXW7 expression in a panel of T-ALL patient-derived xenografts. Finally, we show that miR-223 inhibition prevents T-ALL resistance to γ-secretase inhibitor (GSI) treatment, suggesting that miR-223 could be involved in GSI sensitivity and its inhibition may be exploited in target therapy protocols.

Controlling wetting and self-assembly dynamics by tailored hydrophobic and oleophobic surfaces.

Tailored hydrophobic and oleophobic surfaces are exploited for controlling the wetting behaviour and evaporation process of solution dropped on them. This enables molecules and nano-objects that are dissolved in water or organic solvents to be delivered and arranged in a well-defined 2D layout.

3D vertical nanostructures for enhanced infrared plasmonics

The exploitation of surface plasmon polaritons has been mostly limited to the visible and near infrared range, due to the low frequency limit for coherent plasmon excitation and the reduction of confinement on the metal surface for lower energies. In this work we show that 3D - out of plane - nanostructures can considerably increase the intrinsic quality of the optical output, light confinement and electric field enhancement factors, also in the near and mid-infrared. We suggest that the physical principle relies on the combination of far field and near field interactions between neighboring antennas, promoted by the 3D out-of-plane geometry. We first analyze the changes in the optical behavior, which occur when passing from a single on-plane nanostructure to a 3D out-of-plane configuration. Then we show that by arranging the nanostructures in periodic arrays, 3D architectures can provide, in the mid-IR, a much stronger plasmonic response, compared to that achievable with the use of 2D configurations, leading to higher energy harvesting properties and improved Q-factors, with bright perspective up to the terahertz range.

Direct Synthesis of Carbon-Doped TiO2–Bronze Nanowires as Anode Materials for High Performance Lithium-Ion Batteries

Carbon-doped TiO2-bronze nanowires were synthesized via a facile doping mechanism and were exploited as active material for Li-ion batteries. We demonstrate that both the wire geometry and the presence of carbon doping contribute to the high electrochemical performance of these materials. Direct carbon doping for example reduces the Li-ion diffusion length and improves the electrical conductivity of the wires, as demonstrated by cycling experiments, which evidenced remarkably higher capacities and superior rate capability over the undoped nanowires. The as-prepared carbon-doped nanowires, evaluated in lithium half-cells, exhibited lithium storage capacity of ∼306 mA h g(-1) (91% of the theoretical capacity) at the current rate of 0.1C as well as excellent discharge capacity of ∼160 mAh g(-1) even at the current rate of 10 C after 1000 charge/discharge cycles.

Next-generation textiles: from embedded supercapacitors to lithium ion batteries

This review summarizes the cutting edge advances in the field of textile-based energy storage devices with particular emphasis on the nature and preparation of electrode materials for both supercapacitors and lithium ion batteries. Indeed, due to the overwhelming increase of the worldwide demand for high-tech products, energy storage has become one of the most up-to-date debating topics. In this regard, and considering also the well-known environmental issues often related to the fabrication of new energy products, it is important for the scientific community to develop new electrochemical energy storage systems based on eco-efficient synthetic processes and capable of serving the needs of the next generation of electronics. To this end, textile-based energy storage devices are emerging as a viable alternative to their conventional rigid counterparts. These devices have to be flexible, lightweight and should be compatible with futuristic miniaturized electronic gadgets. We have discussed how supercapacitors and Li-ion batteries are combined with textiles to realize flexible and wearable storage devices. The most important parameters, both from the electrochemical and textile points of view, have been taken into account in order to provide, as much as possible, a standard reference for comparing different kinds of textile-based energy storage devices. These parameters include electrode fibers configuration, fiber diameter, tensile strength, capacitance, charge/discharge capacity, Coulombic efficiency and capacity retention. Furthermore, in this review textile electrodes have been classified into two categories, according to the fabrication strategies: bottom-up and top-down fabrication processes. To conclude, the main aim of this review is to provide an organic outline of the recent research progress and perspectives on textile-based energy storage devices.

Bio-inspired hybrid microelectrodes: a hybrid solution to improve long-term performance of chronic intracortical implants

The use of implants that allow chronic electrical stimulation and recording in the brain of human patients is currently limited by a series of events that cause the deterioration over time of both the electrode surface and the surrounding tissue. The main reason of failure is the tissue inflammatory reaction that eventually causes neuronal loss and glial encapsulation, resulting in a progressive increase of the electrode-electrolyte impedance. Here, we describe a new method to create bio-inspired electrodes to mimic the mechanical properties and biological composition of the host tissue. This combination has a great potential to increase the implant lifetime by reducing tissue reaction and improving electrical coupling. Our method implies coating the electrode with reprogrammed neural or glial cells encapsulated within a hydrogel layer. We chose fibrin as a hydrogel and primary hippocampal neurons or astrocytes from rat brain as cellular layer. We demonstrate that fibrin coating is highly biocompatible, forms uniform coatings of controllable thickness, does not alter the electrochemical properties of the microelectrode and allows good quality recordings. Moreover, it reduces the amount of host reactive astrocytes – over time – compared to a bare wire and is fully reabsorbed by the surrounding tissue within 7 days after implantation, avoiding the common problem of hydrogels swelling. Both astrocytes and neurons could be successfully grown onto the electrode surface within the fibrin hydrogel without altering the electrochemical properties of the microelectrode. This bio-hybrid device has therefore a good potential to improve the electrical integration at the neuron-electrode interface and support the long-term success of neural prostheses.

Writing and Functionalisation of Suspended DNA Nanowires on Superhydrophobic Pillar Arrays

Nanowire arrays and networks with precisely controlled patterns are very interesting for innovative device concepts in mesoscopic physics. In particular, DNA templates have proven to be versatile for the fabrication of complex structures that obtained functionality via combinations with other materials, for example by functionalisation with molecules or nanoparticles, or by coating with metals. Here, the controlled motion of the a three-phase contact line (TCL) of DNA-loaded drops on superhydrophobic substrates is used to fabricate suspended nanowire arrays. In particular, the deposition of DNA wires is imaged in situ, and different patterns are obtained on hexagonal pillar arrays by controlling the TCL velocity and direction. Robust conductive wires and networks are achieved by coating the wires with a thin layer of gold, and as proof of concept conductivity measurements are performed on single suspended wires. The plastic material of the superhydrophobic pillars ensures electrical isolation from the substrate. The more general versatility of these suspended nanowire networks as functional templates is outlined by fabricating hybrid organic-metal-semiconductor nanowires by growing ZnO nanocrystals onto the metal-coated nanowires.