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Photodynamic therapy (PDT) is a minimally invasive potential therapeutic intervention for cancer, which has become a subject of interest in recent decades. PDT involves three components: light, oxygen, and a photosensitizer. When irradiated with light of a suitable wavelength, a photosensitizer absorbs the energy and generates reactive oxygenated species (ROS) or singlet oxygen (SO), responsible for the cell-killing and therapeutic effects. PDT, however, is ineffective for tumors located deep under the skin due to the short penetration depth in tissues of the visible light required by conventional photosensitizers. A potential solution to remove this drawback is the use of nanoscintillators. Upon x-rays excitation, the light generated by the nanoscintillators activates the photosensitizers through energy transfer to produce SO [1]. X-ray-activated PDT(X-PDT) therefore combines radio- and photo-dynamic therapies for a more efficient tumor destruction. We present the results on hybrid fluorescent nanotubes working as X-PDT agents. An ionic self-assembly strategy is used to functionalize the surface of inorganic chrysotile scintillating nanotubes ( Mg3Si2O5(OH)4 ) with efficient SO-sensitizer dyes, whose properties are preserved from the in vitro to the in vivo condition [2]. The occurrence of energy transfer from the chrysotile to different photosensitizers (Bengal Rose, Erythrosine B and porphyrin TPPS4) has been verified, together with the subsequent production of 1O2 under X-ray excitation. Finally, in vitro experiments are reported to verify the low cytotoxicity associated with the presence of functionalized nanotubes in the cellular environment. Therefore, chrysotile nanotubes can be considered as promising materials to be used as nanoscintillator for X-PDT.

The formation of lithium dendrites represents one of the main issues in the use of lithium anode for rechargeable batteries. To block their growth a possible solution is to increase the Young’s modulus of the electrolytes by creating hybrid ceramic-polymer systems [1]. Our approach is the realization of small polymer-chain-grafted nanoparticles (NP) as a branched structure filler which gives a better chemistry affinity with the polymer matrix and increases its mechanical resistance [2]. In particular, here we investigate PEO5K-grafted TiO2 NP as a filler for PEO4M/ LiTFSI-based Solid Polymer Electrolyte.

As a model radio-photodynamic therapy (RPDT) agent, we developed a multicomponent nanomaterial by anchoring conjugated chromophores on the surface of scintillating chrysotile nanotubes. Its ultimate composition makes the system a scintillation-activated photosensitizer for the singlet oxygen production. This nanomaterial shows a remarkable ability to enhance the production of singlet oxygen in an aqueous environment, under X-ray irradiation, boosting its production by almost 1 order of magnitude. Its efficiency as a coadjutant for radiotherapy has been tested in vitro, showing a striking efficacy in enhancing both the prompt cytotoxicity of the ionizing radiation and the long-term cytotoxicity given by radiation-activated apoptosis. Notably, the beneficial activity of the RPDT agent is prominent at low levels of delivered doses comparable to the one employed in clinical treatments. This opens the possibility of effectively reducing the therapy exposure and consequently undesired collateral effects due to prolonged exposure of patients to high-energy radiation.

La decorazione superficiale è un metodo molto utile che permette di migliorare le prestazioni di materiali nanocompositi polimerici, in quanto agisce sull'incompatibilità tra la fase organica e quella inorganica. L'introduzione di un sottile strato polimerico consente una migliore dispersione di nanocristalli inorganici (NC) in matrici polimeriche, dove al contrario particelle nude aggregano e precipitano. Inoltre, la modifica superficiale è uno metodo efficace che permette di introdurre funzionalità aggiuntive ai NC, offrendo nuove proprietà per un gran numero di applicazioni. Durante il mio periodo di ricerca ho sintetizzato NC di biossido di titanio di diverse fasi e dimensioni e ho studiato il comportamento delle nanoparticelle in acqua con TD NMR. Abbiamo osservato che l'acqua interagisce con la superficie in modo tale da diventare una sonda in grado di identificare la fase cristallina del NC. In seguito, è stato condotto uno studio sul processo di grafting to su anatase sferico di polietilenossido monometiletere (mPEO) commerciale e polistirene (PS), sintetizzato tramite polimerizzazione RAFT. I polimeri sono stati modificati con diversi gruppi ancoranti. Gli esperimenti sono stati condotti utilizzando diversi solventi e condizioni sperimentali. Dal momento che abbiamo a che fare con un sistema composto da tre componenti, controllando le interazioni polimero-solvente, la reattività della superficie e l'interazione superficie-solvente, è stato possibile regolare la densità delle catene polimeriche legate e di conseguenza la loro conformazione. Successivamente è stata affrontata la preparazione di nanocompositi a base di poliuretano termoplastico (TPU) a partire da un sistema mixed double layer su anatase rodlike. È stata utilizzata una sintesi colloidale che si adatta alle esigenze di buon controllo sulla dimensione e sulla purezza del cristallo con la produzione su larga scala. Le particelle prodotte, ricoperte da acido oleico (OA), sono successivamente decorate con approccio grafting to utilizzando mPEO ad alto peso molecolare. Le nanoparticelle presentano uno strato ad alta densità di OA e uno a bassa densità di mPEO. In seguito, sono stati preparati per solvent catsing una serie di materiali nanocompositi basati su un double layer mPEO-OA@Anatase e single layer OA @ Anatase in TPU altamente alifatico. Sono stati ottenuti film otticamente trasparenti con indice di rifrazione più elevato (1.63) rispetto al TPU non caricato (1.49). Le prove meccaniche dei materiali nanocompositi hanno mostrato moduli elastici migliori rispetto al semplice TPU. In particolare, il mPEO-OA@Anatase, a parità di quantitativo di filler, ha mostrato un modulo elastico più elevato rispetto all’OA@Anatase. Infine, ho trascorso 7 mesi presso il gruppo del Dr. Benicewicz nella University of South Carolina (USA) in cui ho lavorato su un progetto focalizzato sulla sintesi di membrane polimeriche composte da materiale nanocomposito in grado di separare efficacemente miscele di gas. La prima parte del progetto è stata la preparazione di una serie di campioni basati su particelle di fumed silca (FS) utilizzando un approccio grafting-from con polimetilacrilato. In letteratura è riportato che nanocristalli graftati con polimeri, se in grado di riorganizzarsi ordinatamente nello spazio, possiedono migliori proprietà di permeabilità. Questo è legato al controllo sulla formazione di volume libero nel materiale. Si è osservato che le FS non sono in grado di riorganizzarsi ordinatamente e i dati sperimentali hanno confermato che questo sistema si comporta come una barriera fisica ai gas. Nella seconda parte del progetto è stata sintetizzato un nanocomposito con migliore permeabilità e selettività alla CO2. Questo materiale è stato ottenuto sfruttando la combinazione dell'effetto self-assembly, utilizzano NP di silice, e l'uso di un polimero più selettivo (metacrilammide con catena laterale oligoaniline) sintetizzato ad hoc. Surface ligand engineering is an effective tool used to enhance polymer nanocomposites materials performance, since it plays a key role on one of the trickiest issues: the incompatibility between the organic and inorganic phase. The introduction of a thin polymeric layer enables a good dispersion of the inorganic nanocrystals (NCs) in polymer matrices, where otherwise bare particles aggregate and precipitate. The surface modification is an effective method to introduce additional functionalities to the NPs, giving new properties for a large number of applications. During my research I synthesized different titanium dioxide NCs of different phase and size. I investigated the behavior of bare TiO2 NCs in water. Taking advantage of the interaction between water molecules and titanium dioxide NCs, we found that water interacts in a way that make it a probe able to identify the titanium dioxide crystalline phase. Then an intensive study was done to understand the role of solvents during the grafting process in terms of interaction with polymer chains and inorganic surface. At first a study was done on the grafting-to process of polyethylene oxide monomethylether (mPEO) and polystyrene (PS) on spherical anatase NCs. Commercial mPEO of different molecular weight and polystyrene, synthesized via RAFT polymerization, were used and modified with different anchoring group. The polymers were grafted on anatase NCs through grafting-to approach using different solvents and experimental conditions. Water and methylene chloride were selected according to their ability to interact with the polymer chains and the NC’s surface. Thanks to this massive work we improved our knowledge on the grafting-to approach; we produced a method to create NCs with controlled graft densities and well-defined conformations. Thanks to our experience built during these years of research activity, we were able to prepare a nanocomposite material based on thermoplastic polyurethane (TPU). We started from a mixed double layer system tethered on rod-like anatase nanocrystal. The NCs covered with oleic acid (OA) were synthesized with a colloidal process and modified with a grafting-to approach using a high molecular weight mPEO. The as synthesized object is composed by a high density layer of OA and a low density layer of mPEO (mPEO-OA@Anatase). In order to investigate the properties of this type of objects, a set of nanocomposite materials based on mPEO-OA@Anatase and OA@Anatase were produced in a highly aliphatic TPU matrix with a solvent casting process. It was observed that for both mPEO-OA@Anatase and OA@Anatase optically clear films with improved refractive index (1.63) were obtained. The mechanical tests showed better elastic modulus for filler loaded nanocomposite materials. In particular the mPEO-OA@Anatase presented a higher elastic modulus than OA@Anatase when loaded with the same amount of nanofiller without affecting the optical properties. During my research period abroad, I spent 7 months at Dr. Benicewicz’s group in the University of South Carolina (USA). The aim of my project was focused on the synthesis of new nanocomposite material in the gas separation field. In the first part of the project we prepared a set of samples based on fumed silica (FS) particles using a grafting-from approach to modify the surface with RAFT polymerization. This kind of particles were not able to self-assemble in an organized and no improvement of the the gas permeation properties, even if FS were well dispersed into the polymer matrix. Experimental data confirmed that FS acts as a physical gas barrier. In the second part of the project were synthesized a nanocomposite material using the same approach on silica NP with polymethacrylamide with oligoaniline side chain. These NPs were able to self-assemble in a controlled fashion and thanks to a more selective polymer we obtained a material with enhanced permeability and selectivity to CO2.

Reversible addition-fragmentation chain transfer polymerization of chloroprene on the surface of silica nanoparticles was performed to obtain polychloroprene-grafted-silica nanoparticles (PCP-g-SiO2 NPs). These particles were dispersed in a commercial polychloroprene matrix to obtain PCP nanocomposites with different silica core loadings (1, 5, 10, and 25 wt%). Two different chain graft densities were studied (“low,” 0.022 ch/nm2 and “high,” 0.21 ch/nm2) as a function of the grafted polymer molecular mass. The cured samples showed significant improvement in the mechanical properties of the PCP rubber nanocomposites as compared to the unfilled PCP as measured by standard tensile and dynamic mechanical analysis even with low silica content. The mechanical properties of the nanocomposites were notably enhanced when the graft density was low and grafted molecular masses were high. Transmission electron microscopy (TEM) and Small-Angle X-ray Scattering (SAXS) were used to analyze the dispersion states of the grafted nanoparticles which confirmed the correlation between high grafted chain lengths and improved dispersion states and mechanical properties.

Nanocrystals (NCs) surface characterization is a fundamental step for understanding the physical and chemical phenomena involved at the nanoscale. Surface energy and chemistry depend on particle size and composition, and, in turn, determine the interaction of NCs with the surrounding environment, their properties and stability, and the feasibility of nanocomposites. This work aims at extracting more information on the surface of different titanium dioxide polymorphs using1H-TD-NMR of water. Taking advantage of the interaction between water molecules and titanium dioxide NCs, it is possible to correlate the proton transverse relaxation times (T2) as the function of the concentration and the specific surface area (δp·Cm) and use it as an indicator of the crystal phase. Examples of three different crystals phase, rutile, anatase, and brookite, have been finely characterized and their behavior in water solution have been studied with TD-NMR. The results show a linear correlation between relaxivity (R2) and their concentration Cm. The resulting slopes, after normalization for the specific surface, represent the surface/water interaction and range from 1.28 g m-2s-1of 50 nm rutile nanocrystals to 0.52 for similar sized brookite. Even higher slopes (1.85) characterize smaller rutile NCs, in qualitative accordance with the trends of surface energy. Thanks to proton relaxation phenomena that occur at the NCs surface, it is possible to differentiate the crystal phase and the specific surface area of titanium dioxide polymorphs in water solution.

PEGylation of metal oxide nanoparticles is the common approach to improve their biocompatibility and in vivo circulation time. In this work, we present a combined experimental and theoretical study to determine the operating condition that guarantee very high grafting densities, which are desirable in any biomedical application. Moreover, we present an insightful conformational analysis spanning different coverage regimes and increasing polymer chain lengths. Based on 13C NMR measurements and molecular dynamics simulations, we show that classical and popular models of polymer conformation on surfaces fail in determining the mushroom-to-brush transition point and prove that it actually takes place only at rather high grafting density values.