Ilaria E. Palamà
University of Salento
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Publication
Featured researches published by Ilaria E. Palamà.
Journal of the American Chemical Society | 2011
Ilaria E. Palamà; Francesca Di Maria; Ilenia Viola; Eduardo Fabiano; Giuseppe Gigli; Cristian Bettini; Giovanna Barbarella
In our search for thiophene fluorophores that can overcome the limits of currently available organic dyes in live-cell staining, we synthesized biocompatible dithienothiophene-S,S-dioxide derivatives (DTTOs) that were spontaneously taken up by live mouse embryonic fibroblasts and HeLa cells. Upon treatment with DTTOs, the cells secreted nanostructured fluorescent fibrils, while cell viability remained unaltered. Comparison with the behavior of other cell-permeant, newly synthesized thiophene fluorophores showed that the formation of fluorescent fibrils was peculiar to DTTO dyes. Laser scanning confocal microscopy of the fluorescent fibrils showed that most of them were characterized by helical supramolecular organization. Electrophoretic analysis and theoretical calculations suggested that the DTTOs were selectively recognized by the HyPro component of procollagen polypeptide chains and incorporated through the formation of multiple H-bondings.
Nanomedicine: Nanotechnology, Biology and Medicine | 2010
Ilaria E. Palamà; Stefano Leporatti; Emanuela de Luca; Nicola Di Renzo; Michele Maffia; Carlo Gambacorti-Passerini; R. Rinaldi; Giuseppe Gigli; Roberto Cingolani; Addolorata Ml Coluccia
AIM The lack of sensitivity of chronic myeloid leukemia (CML) stem cells to imatinib mesylate (IM) commonly leads to drug dose escalation or early disease relapses when therapy is stopped. Here, we report that packaging of IM into a biodegradable carrier based on polyelectrolyte microcapsules increases drug retention and antitumor activity in CML stem cells, also improving the ex vivo purging of malignant progenitors from patient autografts. MATERIALS & METHODS Microparticles/capsules were obtained by layer-by-layer (LbL) self-assembly of oppositely charged polyelectrolyte multilayers on removable calcium carbonate (CaCO(3)) templates and loaded with or without IM. A leukemic cell line (KU812) and CD34(+) cells freshly isolated from healthy donors or CML patients were tested. RESULTS & DISCUSSION Polyelectrolyte microcapsules (PMCs) with an average diameter of 3 microm, fluorescently labelled multilayers sensitive to the action of intracellular proteases and 95-99% encapsulation efficiency of IM, were prepared. Cell uptake efficiency of such biodegradable carriers was quantified in KU812, leukemic and normal CD34(+) stem cells (range: 70-85%), and empty PMCs did not impact cell viability. IM-loaded PMCs selectively targeted CML cells, by promoting apoptosis at doses that exert only cytostatic effects by IM alone. More importantly, residual CML cells from patient leukapheresis products were reduced or eliminated more efficiently by using IM-loaded PMCs compared with freely soluble IM, with a purging efficiency of several logs. No adverse effects on normal CD34(+) stem-cell survival and their clonogenic potential was noticed in long-term cultures of hematopoietic progenitors in vitro. CONCLUSION This pilot study provides the proof-of-principle for the clinical application of biodegradable IM-loaded PMC as feasible, safe and effective ex vivo purging agents to target CML stem cells, in order to improve transplant outcome of resistant/relapsed patients or reduce IM dose escalation.
Blood | 2012
Giovanni Reddiconto; Claudia Toto; Ilaria E. Palamà; Simone De Leo; Emanuela de Luca; Serena De Matteis; Luciana Dini; Carlo Gambacorti Passerini; Nicola Di Renzo; Michele Maffia; Addolorata Coluccia
The targeting of BCR-ABL, a hybrid oncogenic tyrosine (Y) kinase, does not eradicate chronic myeloid leukemia (CML)-initiating cells. Activation of β-catenin was linked to CML leukemogenesis and drug resistance through its BCR-ABL-dependent Y phosphorylation and impaired binding to GSK3β (glycogen synthase kinase 3β). Herein, we show that GSK3β is constitutively Y(216) phospho-activated and predominantly relocated to the cytoplasm in primary CML stem/progenitor cells compared with its balanced active/inactive levels and cytosolic/nuclear distribution in normal cells. Under cytokine support, persistent GSK3β activity and its altered subcellular localization were correlated with BCR-ABL-dependent and -independent activation of MAPK and p60-SRC/GSK3β complex formation. Specifically, GSK3β activity and nuclear import were increased by imatinib mesylate (IM), a selective ABL inhibitor, but prevented by dasatinib that targets both BCR-ABL- and cytokine-dependent MAPK/p60-SRC activity. SB216763, a specific GSK3 inhibitor, promoted an almost complete suppression of primary CML stem/progenitor cells when combined with IM, but not dasatinib, while sparing bcr-abl-negative cells. Our data indicate that GSK3 inhibition acts to prime a pro-differentiative/apoptotic transcription program in the nucleus of IM-treated CML cells by affecting the β-catenin, cyclinD1, C-EBPα, ATF5, mTOR, and p27 levels. In conclusion, our data gain new insight in CML biology, indicating that GSK3 inhibitors may be of therapeutic value in selectively targeting leukemia-initiating cells in combination with IM but not dasatinib.
Journal of Materials Chemistry | 2015
Ilaria E. Palamà; Stefania D'Amone; Valentina Arcadio; Daniela Caschera; R. G. Toro; G. Gigli; Barbara Cortese
Underwater wettability and wetting transitions of non-polar liquids with rough solid surfaces are herein presented. Here, we demonstrate that a hydrophobic/oleophilic surface when immersed in water can result in an oleophilic or “Cassie” state of oil-wetting. This was achieved by utilizing respectively a diamond like carbon (DLC) coating on a cotton substrate and a combination of DLC and zinc oxide (ZnO) nanorods embedded into the structure. Moreover by increasing the time of immersion the oleophilic state reverted to a Wenzel state evolving to Cassies regime. The mechanism of the transition was identified with the diffusion of the air into the water from the trapped air pockets of the substrate interface. Finally, switchable wettability of ZnO/DLC coated substrates allows a promising oil–water separation use.
Journal of Materials Chemistry | 2014
Ilaria E. Palamà; Stefania D'Amone; Mariano Biasiucci; G. Gigli; Barbara Cortese
Oil spills at sea are a severe global environmental issue. Smart materials with controllable wettability are of global challenging interest in oil–water related applications. Nature offers a versatile platform of remarkable hierarchical structures with a chemical component, which provides bioinspired solutions for solving many challenges. In this study, an approach to achieve robust superhydrophobic/oleophobic property on flexible polydimethylsiloxane (PDMS) surfaces which mimics the hierarchical morphology of the natural lotus leaf surface is shown. The structure is prepared by hydrothermal assembly of zinc oxide nanorods onto the microstructured surface, which results in an underwater superoleophobic surface with an oil contact angle up to 153° which can effectively prevent the surface from being polluted by oils. Our results are significant in terms of their importance to academic research and industrial applications and may lead to an innovative impact in the science field.
Organic and Biomolecular Chemistry | 2014
F. Di Maria; Ilaria E. Palamà; Massimo Baroncini; Andrea Barbieri; A. Bongini; R. Bizzarri; G. Gigli; G. Barbarella
A structurally correlated series of cell-permeant thiophene fluorophores, characterized by intense green or red fluorescence inside live mouse embryonic fibroblasts, was developed. The fluorophores displayed rapid internalization, excellent retention inside the cells, and high optical stability in the cytosolic environment and did not alter cell viability and reproducibility. Depending on the molecular structure, they experienced distinct fate inside the cells: from bright and lasting staining of the cytoplasm to selective tagging of a small set of globular proteins.
Journal of drug delivery | 2011
Ilaria E. Palamà; Mariarosaria Musarò; Addolorata Coluccia; Stefania D'Amone; Giuseppe Gigli
This pilot study provides the proof of principle for biomedical application of novel polyelectrolyte complexes (PECs) obtained via electrostatic interactions between dextran sulphate (DXS) and poly(allylamine hydrochloride) (PAH). Scanning electron microscopy (SEM) and atomic force microscopy (AFM) showed that DXS/PAH polyelectrolyte complexes were Monodispersed with regular rounded-shape features and average diameters of 250 nm at 2 : 1 weight ratios of DXS/PAH. Fluorescently labelled DXS and fluorescein-isothiocyanate- (FITC-)conjugate DXS were used to follow cell uptake efficiency of PECs and biodegradability of their enzymatically degradable DXS-layers by using confocal laser scanning microscopy (CLSM). Moreover, quantitative MTT and Trypan Blue assays were employed to validate PECs as feasible and safe nanoscaled carriers at single-cell level without adverse effects on metabolism and viability.
MedChemComm | 2015
Barbara Cortese; Stefania D'Amone; G. Gigli; Ilaria E. Palamà
Imatinib mesylate (IM) is an inhibitor that targets the tyrosine kinase activity of BCR-ABL present in Chronic Myeloid Leukemia (CML). Here, IM–chitosan complex loaded poly(e-caprolactone) (PCL) nanoparticles (NPs) are recommended for their potential in supporting controlled release and improving the chemotherapeutic efficiency of IM. The nanoparticles with a size of about 247 nm have a core–shell structure with an IM-containing inner core surrounded by a PCL layer. The presence of chitosan (CH) allows one to modulate the release kinetics in a pH-dependent manner. IM is released from the NPs much more quickly at pH 4.0 and 6.0 than at pH 7.4, which is a desirable characteristic for cancer-targeted drug delivery. Our core–shell PCL NPs could provide a simple and easy way to allow controlled release of IM and improve their chemotherapeutic efficiency, combining the pH sensibility of CH and the slow degradation of PCL.
Journal of Materials Chemistry B | 2015
Ilaria E. Palamà; Francesca Di Maria; Stefania D'Amone; Giovanna Barbarella; G. Gigli
Live cells can form multifunctional and environmentally responsive multiscale assemblies of living and non-living components. We recently reported the results of a unique approach to introduce supplementary properties, fluorescence in particular, into fibrillar proteins produced by live fibroblasts and extruded into the ECM. In this work, we demonstrate that the physiological secretion of fluorescent nanostructured microfibers upon the spontaneous uptake of the appropriate fluorophore extends to living cells derived by different tissue contexts. We also show that live cells seeded on fluorescent microfibers have a different fate in terms of the cellular morphology, cytoskeleton rearrangement and viability. These results suggest that the microfibers, which are biocompatible and biodegradable, can be used as multiscale biomaterials to direct the cell behaviour.
Integrative Biology | 2013
Ilenia Viola; Ilaria E. Palamà; Addolorata Coluccia; Mariano Biasiucci; Barbara Dozza; Enrico Lucarelli; Francesca Di Maria; Giovanna Barbarella; Giuseppe Gigli
We have recently reported initial results concerning an original approach to introduce additional properties into fibrillar proteins produced by live fibroblasts and extruded into the ECM. The key to such an approach was biocompatible, fluorescent and semiconducting synthetic molecules which penetrated spontaneously the cells and were progressively encompassed via non-bonding interactions during the self-assembly process of the proteins, without altering cell viability and reproducibility. In this paper we demonstrate that the intracellular secretion of fluorescent microfibers can be generalized to living primary and immortalized human/mouse fibroblasts. By means of real-time single-cell confocal microscopy we show that the fluorescent microfibers, most of which display helical morphology, are generated by intracellular coding of the synthetic molecules. We also describe co-localization experiments on the fluorescent microfibers isolated from the cell milieu demonstrating that they are mainly made of type-I collagen. Finally, we report experimental data indicating that the embedded synthetic molecules cause the proteins not only to be fluorescent but also capable of electrical conductivity.