Magnetic nanobeads decorated by thermo-responsive PNIPAM shell as medical platforms for the efficient delivery of doxorubicin to tumour cells

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

Multifunctional nanostructures based on inorganic nanoparticles and oligothiophenes and their exploitation for cellular studies.

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

Acidic pH-responsive nanogels as smart cargo systems for the simultaneous loading and release of short oligonucleotides and magnetic nanoparticles.

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

Development of a navigation algorithm for autonomous underwater vehicles

In this paper, the authors present an underwater navigation system for Autonomous Underwater Vehicles (AUVs) which exploits measurements from an Inertial Measurement Unit (IMU), a Pressure Sensor (PS) for depth and the Global Positioning System (GPS, used during periodic and dedicated resurfacings) and relies on either the Extended Kalman Filter (EKF) or the Unscented Kalman Filter (UKF) for the state estimation. Both (EKF and UKF) navigation algorithms have been validated through experimental navigation data related to some sea tests performed in La Spezia (Italy) with one of Typhoon class vehicles during the NATO CommsNet13 experiment (held in September 2013) and through Ultra-Short BaseLine (USBL) fixes used as a reference (ground truth). Typhoon is an AUV designed by the Department of Industrial Engineering of the Florence University for exploration and surveillance of underwater archaeological sites in the framework of the Italian THESAURUS project and the European ARROWS project. The obtained results have demonstrated the effectiveness of both navigation algorithms and the superiority of the UKF (very suitable for AUV navigation and, up to now, still not used much in this field) without increasing the computational load (affordable for on-line on-board AUV implementation)

Conformable nanowire-in-nanofiber hybrids for low-threshold optical gain in the ultraviolet

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.Comment: 50 pages, 17 figures, 1 table, ACS Nano, 202

Tailoring of silica-based nanoporous pod by spermidine multi-activity

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

Scaling Up Magnetic Nanobead Synthesis with Improved Stability for Biomedical Applications

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

Magnetic nanocarriers with tunable pH dependence for controlled loading and release of cationic and anionic payloads.

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

Rod-shaped nanostructures based on superparamagnetic nanocrystals as viscosity sensors in liquid

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/110/6/10.1063/1.3638695Superparamagnetic 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)

Magnetic-Fluorescent Colloidal Nanobeads: Preparation and Exploitation …

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