Search

The reactivity of alkylidene malonamides as Michael receptors in the conjugate addition of N,O - bis(trimethylsilyl)hydroxylamine has been explored . Due to the presence of several different functionalities that may be selectively transformed, the products of the conjugate addition represent versatile intermediates for the synthesis of isoxazolidinones, aziridines, oxazolines or highly functionalized β-amino-amide derivatives. These novel molecules possessing unusual backbones may be exploited as scaffolds in the preparation of bioactive molecules.

Very monodisperse water-soluble silica core-surfactant shell nanoparticles (SCSS NPs) doped with a rhodamine B derivative were prepared using micelles of F127 as nanoreactors for the hydrolysis and condensation of the silica precursor tetraethoxysilane (TEOS). The functionalization of the rhodamines with a triethoxysilane group allowed the covalent binding of the fluorophores to the silica core: no leaking of the dye was observed when the NPs were purified either by ultrafiltration (UF) or dialysis. The diameter of the core (d(c) = 10 ± 1 nm) was determined by TEM and subtracted from the hydrodynamic diameter, measured by DLS, (d(H) = 24 nm, PdI = 0.1) to calculate the shell thickness (∼7 nm). The presence of a single population of NPs with a radius compatible with the one measured by DLS after UF was confirmed by AF4-MALS-RI measurements. The concentration of the NPs was measured by MALS-RI. This allowed us to determine the average number of rhodamine molecules per NP (10). The ability of the NPs to host hydrophobic species as cyanines in the SS was confirmed by fluorescence anisotropy measurements. Steady-state and time-resolved fluorescence measurements allowed us to observe the occurrence of a very efficient Förster resonance energy transfer process from the covalently linked rhodamines to the hosted cyanines. In particular, the analysis of the TCSPC data and steady-state measurements revealed that the adsorption of a single cyanine molecule causes an almost complete quenching of the fluorescence of the NP. Thanks to these observations, it was possible to easily determine the concentration of the NPs by fluorescence titration experiments. Results are in good agreement with the concentration values obtained by MALS-RI. Finally, the hosted cyanine molecule could be extracted with (±)-2-octanol, demonstrating the reversibility of the adsorption process.

Marco Soster,1,* Riccardo Juris,2,* Sara Bonacchi,2 Damiano Genovese,2 Marco Montalti,2 Enrico Rampazzo,2 Nelsi Zaccheroni,2 Paolo Garagnani,2 Federico Bussolino,3,4 Luca Prodi,2 Serena Marchiò1,4 1Institute for Cancer Research and Treatment, Laboratory of Tumor Microenvironment and University of Torino, Department of Oncological Sciences, Candiolo, 2University of Bologna, Department of Chemistry "G.Ciamician", Bologna, 3Institute for Cancer Research and Treatment, Laboratory of Vascular Oncology and University of Torino, Department of Oncological Sciences, Candiolo, 4APAvadis Biotechnologies, BioIndustry Park S Fumero, Colleretto Giacosa, Italy*These authors equally contributed to the workBackground and methods: Despite the recent introduction of targeted bio-drugs, the scarcity of successful therapeutic options for advanced colorectal cancer remains a limiting factor in patient management. The efficacy of curative surgical interventions can only be extended through earlier detection of metastatic foci, which is dependent on both the sensitivity and specificity of the diagnostic tools.Results: We propose a high-performance imaging platform based on silica-poly(ethylene glycol) nanoparticles doped with rhodamine B and cyanine 5. Simultaneous detection of these dyes is the basis for background subtraction and signal amplification, thus providing high-sensitivity imaging. The functionalization of poly(ethylene glycol) tails on the external face of the nanoparticles with metastasis-specific peptides guarantees their homing to and accumulation at target tissues, resulting in specific visualization, even of submillimetric metastases.Conclusions: The results reported here demonstrate that our rationally designed modular nanosystems have the ability to produce a breakthrough in the detection of micrometastases for subsequent translation to clinics in the immediate future.Keywords: colorectal cancer, imaging platform, luminescent targeting, micrometastasis, peptide targeting

Biocompatible highly bright silica nanoparticles were designed, prepared and tested in small living organisms for both in vivo and ex vivo imaging. The results that we report here demonstrate that they are suitable for optical imaging applications as a possible alternative to commercially available fluorescent materials including quantum dots. Moreover, the tunability of their photophysical properties, which was enhanced by the use of different dyes as doping agents, constitutes a very important added value in the field of medical diagnostics.

Devices are systems able to performs specific functions[1] which result from the coordinated operation of different components. The design of these systems is hence based on the identification or the development of the necessary parts and in their integration in a suitable supramolecular architecture. The main challenge in such a process is undoubtedly synthetical: the control of the mutual interactions between the molecular active units, in fact, requires a fine tuning of the distance and orientation of the components as well as of the electronic properties of the interconnecting linkers. Organization through covalent bonding has, in this context, several advantages and many examples of covalent supramolecular devices have been reported in the last two decades. Beside the covalent approach led to the design of fascinating and efficient prototypes it often made necessary the preparation of beautiful but complicated chemical systems which resulted from time demanding multistep synthetic paths and that are not suitable for large scale production. Many examples of devices derived from a more traditionally supramolecular approach based on self assembly and host-guest interactions has also been reported. In this chapter some relevant examples of both covalent and self-organizing supramolecular devices based on energy transfer (ET) processes will be reviewed. The basic principles of ET will also be discussed. Recently, the advent of nanomaterials offered to supramolecular chemists new active components and structural platforms suitable for the design of nanometric molecular devices. At the present stage, nanomaterials represents an ideal platform to achieve a reasonable degree of spatial organization especially when the integration of a large number of components is required or desired. This approach allows the achievement of complex, extensive devices otherwise not accessible. Moreover some nanomaterials have unique photophysical properties and can become themselves active nanosized component of the final device. Considered the huge literature in the field of hetero-supramolecular chemistry even when restricted to energy transfer based devices, we decided to focus the last part of this review chapter on discrete nanodevices, namely on systems which can be, at least in principle, isolated as individual nanometric (working) objects.

Seven new bio-inspired chemosensors (2-4 and 7-10) based on fluorescent peptides were synthesized and characterized by elemental analysis, 1H-NMR, 13C-NMR, melting point, matrix assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF-MS), infrared, UV-vis absorption and emission spectroscopy. The interaction with transition and post-transition metal ions (Cu2+, Ni2+, Ag+, Zn2+, Cd2+, Hg2+, Pb2+ and Fe3+) has been explored by absorption and fluorescence emission spectroscopy and MALDI-TOF mass spectrometry. The reported fluorescent peptide systems, introducing biological molecules in the skeleton of the probes, enhance their sensitivity and confer them strong potentials for applications in biological fields. Gold and silica nanoparticles functionalized with these peptides were also obtained. All nanoparticles were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), UV-vis absorption and fluorescence spectroscopy. Stable gold nanoparticles (diameter 2-10 nm) bearing ligands 1 and 4 were obtained by common reductive synthesis. Commercial silica nanoparticles were decorated at their surface using compounds 8 to 10, linked through a silane spacer. The same chemosensors were also taken into aqueous solutions through their dispersion in the outer layer of silica core/PEG shell nanoparticles. In both cases, these complex nanoarchitectures behaved as new sensitive materials for Ag+ and Hg2+ in water. The possibility to use these species in this solvent is particularly valuable since the impact on human health of heavy and transition metal ions pollution is very severe, and all analytical and diagnostics investigations involve a water environment., Fundação para a Ciência e a Tecnologia (FCT), Universidade do Minho (UM)

Silica nanoparticles are versatile platforms with many intrinsic features, such as low toxicity. Proper design and derivatization yields particularly stable colloids, even in physiological conditions, and provides them with multiple functions. A suitable choice of dyes and synthetic strategy may, in particular, yield a very bright nanosystem. Silica nanoparticles thus offer unique potential in the nanotechnology arena, and further improvement and optimization could substantially increase their application in fields of high social and economic impact, such as medical diagnostics and therapy, environmental and food analysis, and security. This paper describes silica-based, multicomponent nanosystems with intrinsic directional energy- and electron- transfer processes, on which highly valued functions like light harvesting and signal amplification are based.

The field of nanoparticles is amazingly many-sided and consequently their applications range between many different areas from industry to bio-analysis and catalysis. In particular, luminescent nanoparticles attract close attention in the areas of biology, medical diagnosis and therapy, where they already find many applications. In this so fascinating and wide framework we have focussed our attention on luminescent silica nanoparticles able to act as sensing materials. We highlight here the importance, especially with the aim of sensing, of gaining precise knowledge and control of their structures; the performance of a chemosensor is, in fact, totally dependent on its design. We then briefly present the state of the art and the progress both in the synthetic protocols and in the application of luminescent silica nanoparticles as chemosensors. We present many recent examples, organized into two main sections, the first dealing with systems presenting the signalling units on the surface (dye coated silica nanoparticles, DCSNs) and the second with systems entrapping the dyes inside the silica matrix (dye doped silica nanoparticles, DDSNs).

The design of fluorescent chemosensors for biologicallyrelevant chemical species has important impacts in many ap-plications, and for this reason it has been the subject ofactive research in many laboratories worldwide. The ach-ievements in this wide research topic have promoted enor-mous steps forwards, for example, in the field of cell biology,thanks to the comprehension of the role of different chemi-cal species in many biological processes. Recently, research-ers have been moving from molecular chemosensors basedon two communicating units, a receptor and a dye, towardmore complex and sophisticated structures, and have triedto push further the limits of sensitivity and selectivity. Manydifferent solutions have been proposed but, among them,sensing systems based on nanoparticles are certainly one ofthe most interesting and promising.

Nanoparticelle di silice drogate con una molteplicità di coloranti caratterizzate da trasferimento di energia ad elevata efficienza e capaci di Stokes Shift modulabile.

Electronic energy transfer is a crucial photophysical process, since it is at the basis of essential natural phenomena such as photosynthesis, as well as of widely spread artificial molecular devices; moreover, it is a very valuable tool for measuring distances at the nanometer level. For artificial systems, the possibility to take profit of energy transfer processes has enormously increased with the advent of supramolecular chemistry,1 and a new additional boost is expected to be observed with the very rapid growth of nanotechnology, in many different fields, ranging from medical diagnostics to solar energy conversion. In the context of nanotechnology, a great and increasing interest is devoted to nanoparticles.2 Nanoparticles can be made of many different materials, including polymers, metals, semiconductors, or a combination of them. Their versatility and different properties have already gained them many industrial applications in a wide range of fields, such as electronics, medicine and material sciences. One of the cut-edge fields in nanoparticle research is the enhancement of biological imaging for medical diagnostics and drug delivery. In this article, we will focus our attention on the potentialities offered by the use of energy transfer processes in dye-doped or dye-coated silica nanoparticles (DDSN or DCSN respectively),3-10 which conjugate a simple and low-cost preparation with the possibility to obtain sophisticated, but robust, multifunctional systems, especially when they are designed as ‘onion-like’, multilayer structures. The design of these systems is not trivial and it has to be carefully studied to be able to foresee the photophysical characteristics of the resulting materials. On the other hand, despite the complexity of these systems, their synthesis is relatively simple and very versatile. These features make them a very powerful tool to obtain very complex and precious functions from low cost and easy to prepare nanoobjects. In the next paragraphs we will present the most common synthetic strategies to obtain dye doped and dye covered silica nanoparticles and discuss many examples, but we would like to start introducing the energy transfer process and its great scientific and applicative importance.

In accordance with a first aspect of the present invention, it is provided a method for the preparation of an active nanoparticle, comprising a mixing step, during which at least one active compound is mixed with molecules of at least one surfactant in an organic solvent; an evaporation step, that is subsequent to the mixing step and during which the organic solvent is evaporated in order to obtain a residue; a reaction step, which is subsequent to the evaporation step and during which molecules of at least one alkoxysilane are added to the residue and silanized in presence of water; the alkoxysilane is chosen between a tetraalkoxysilane and a trialkoxysilane; the surfactant comprising the following structure: Hydro1-Lipo-Hydro2 wherein Lipo indicates a substantially hydrophobic chain, Hydro1 and Hydro2 each indicate a substantially hydrophilic chain. Advantageously, the active compound is substantially lipophilic.

The present invention relates to methods for the preparation of an active particle, active particles and uses of these active particles. The purpose of this invention is to provide active particles, uses of particles and methods for the preparation of particles, which allow overcoming, at least partially, the drawbacks of the state of the art and are, at the same time, easy and economical to implement. According to the present invention the following are provided: active particles, uses of particles and methods for the preparation of particles as specified in the independent claims which follow and, preferably, in any of the claims directly or indirectly dependent on the independent claims.

Nanoparticelle luminescenti e/o elettroattive e/o adatte ad applicazioni di MRI (magnetic resonance imaging) e/o ad applicazioni di PET (positron emission tomography) vengono preparate miscelando composti luminescenti od elettroattivi e copolimeri a blocco (block-copolymers) etilene ossido/propilene ossido in un solvente organico, che viene successivamente evaporato in modo da ottenere un residuo; e facendo idrolizzare-condensare tetraalcossisilani in una soluzione acquosa in presenza del residuo; le nanoparticelle ottenute mostrano un nullo o trascurabile rilascio dei composti luminescenti od elettroattivi e sono utili per applicazioni bio-analitiche e biomediche.

Nanoparticelle luminescenti e/o elettroattive e/o adatte ad applicazioni di MRI (magnetic resonance imaging) e/o ad applicazioni di PET (positron emission tomography) comprendono una micella, la quale presenta una corona circolare idrofilica ed una porzione centrale idrofobica, ed un nocciolo di polisilicato; la micella comprende una pluralità di molecole di un tensioattivo funzionalizzato presentante la seguente struttura: M1-Hydro1-Lipo-Hydro2-M2 in cui Lipo indica una catena idrofobica; Hydro1 ed Hydro2 indicano, ciascuno, una rispettiva catena idrofilica; M1 ed M2 rappresentano rispettive funzionalità di riconoscimento.

Nanoparticelle luminescenti e/o elettroattive e/o adatte ad applicazioni di MRI (magnetic resonance imaging) e/o ad applicazioni di PET (positron emission tomography) vengono preparate facendo idrolizzare-condensare tetraalcossisilani assieme a composti luminescenti od elettroattivi, i quali possono contenere funzionalità alcossisilaniche, in una soluzione acquosa in presenza di copolimeri a blocco (block-copolymers) etilene ossido/propilene ossido; le nanoparticelle ottenute mostrano un nullo o trascurabile rilascio dei composti luminescenti od elettroattivi e sono utili per applicazioni bio-analitiche e biomediche.

Small constrained non-peptidic mols. consisting of a polyfunctionalized rigid core, carrying appendages corresponding to arginine and aspartic acid side chains, have been recently reported to be promising for drug development. In this work, the 5,6-dihydropyridin-2-one was envisaged as a scaffold to turn into potential integrin ligands, introducing a carboxylic acid and a basic appendage. The synthesis and the antiadhesion activity of a small library of peptidomimetics capable to recognize alpha-v-beta-3 and alpha-5-beta-1 integrins has been herein reported.