Quinoline Group Modified Carbon Nanotubes for the Detection of Zinc Ions

Carbon nanotubes (CNTs) were covalently modified by fluorescence ligand (glycine-N-8-quinolylamide) and formed a hybrid material which could be used as a selective probe for metal ions detection. The anchoring to the surface of the CNTs was carried out by the reaction between the precursor and the carboxyl groups available on the surface of the support. Fourier transform infrared spectroscopy (FTIR) and Thermogravimetric analysis (TGA) unambiguously proved the existence of covalent bonds between CNTs and functional ligands. Fluorescence characterization shows that the obtained organic–inorganic hybrid composite is highly selective and sensitive (0.2 μM) to Zn(II) detection

Silica nanoparticles for fluorescence sensing of Zn(II): exploring the covalent strategy

Silica nanoparticles (about 15 nm diameters), which contain a derivative of 6-methoxy-8-(p-toluensulfonamido)- quinoline (TSQ) as a ZnII fluorescent probe covalently linked to the silica network, were prepared and studied as ZnII fluorescent chemosensors. The systems selectively detect ZnII ions in water rich solutions with a submicromolar sensitivity: 0.13 mm concentrations of ZnII can be measured with the only interference of CuII and CdII ions. Compared with free TSQ, the nanoparticles based systems have the advantage that they can be employed in aqueous solutions without aggregation problems while at the same time, they maintain a similar ZnII affinity and sensing ability. Addition of a second, substrate insensitive, fluorophore to the particles leads to the realization of a ratiometric sensor

Amplified fluorescence response of chemosensors grafted onto silica nanoparticles

In conventional fluorescent chemosensors, the recognition of the target by the receptor unit affects the fluorescence properties of a single covalently coupled fluorescent moiety. Here we show for the first time that when a suitable TSQ derivative is densely grafted onto the surface of preformed silica nanoparticles electronic interactions between the individual chemosensor units enable the free units to recognize the state of the surrounding complexed ones. As a result, the fluorescence transduction is not limited to the local site where binding occurs, but it involves a wider region of the fluorophore network that is able to transfer its excitation energy to the complexed units. Such behavior leads to an amplification of the fluorescence signal. What we report here is the first example of amplification in the case an off-on chemosensor due to its organization onto the surface of silica nanoparticles. We also describe a simple general model to approach amplification in multifluorophoric systems based on the localization of the excited states, which is valid for assemblies such as the supramolecular ones where molecular interactions are weak and do not significantly perturb the individual electronic states. The introduction of an amplification factorf in particular allows for a simple quantitative estimation of the amplification effects

Amplified fluorescence response of chemosensors grafted onto silica nanoparticles

In conventional fluorescent chemosensors, the recognition of the target by the receptor unit affects the fluorescence properties of a single covalently coupled fluorescent moiety. Here we show for the first time that when a suitable TSQ derivative is densely grafted onto the surface of preformed silica nanoparticles electronic interactions between the individual chemosensor units enable the free units to recognize the state of the surrounding complexed ones. As a result, the fluorescence transduction is not limited to the local site where binding occurs, but it involves a wider region of the fluorophore network that is able to transfer its excitation energy to the complexed units. Such behavior leads to an amplification of the fluorescence signal. What we report here is the first example of amplification in the case an off-on chemosensor due to its organization onto the surface of silica nanoparticles. We also describe a simple general model to approach amplification in multifluorophoric systems based on the localization of the excited states, which is valid for assemblies such as the supramolecular ones where molecular interactions are weak and do not significantly perturb the individual electronic states. The introduction of an amplification factorf in particular allows for a simple quantitative estimation of the amplification effects

PANCREATIC CANCER (PaCa)-DERIVED SOLUBLE MEDIATORS INDUCE DENDRITIC CELLS (DC) TO ACQUIRE AN IMMUNESUPPRESSIVE PHENOTYPE BY DOWNREGULATING CTLA4

Objective: An altered function of lymphocytes, DC and immature myeloid cells appears to be an hallmark of tumor-mediated immune suppression and the two inhibitory co-stimulatory receptors PDL-1 and CTLA4 might have a role in this context. The aim of the present in vitro study was to assess whether PaCa cells cross-talk with normal mononuclear circulating cells (PBMC) causing them to acquire an immunesuppressive phenotype and to evaluate whether PDL1 and CTLA4 are involved. Methods: PBMC from blood donors were cultured for 4 days in Control (CTL) and in the PaCa cancer cell line Capan1 conditioned media (CM). Lymphocytes subsets (CD4+, CD8+, CD4+CD25+) and CD33+ immature myeloid cells subsets (CD14+/-; HLA-DR+/-) expressing or not PDL1 and/or CTLA4 were analysed by flow cytometry. To assess immunesuppressive function, myeloid cells were FACS sorted and co-coltured with allogenic total T lymphocytes in 1:20 and 1:40 ratio. Total T lymphocytes proliferation was determined by 3HThymidine uptake. Results: Capan1 CM caused an expansion of CD4+CD25+ (p=0.01) and a reduction of CD33+CD14- HLA-DR+ (p=0.03) cells. In this latter cellular subset, CM caused also an increase of PDL1 (p=0.046) and a decrease of CTLA4 (p=0.05) positive cells. FACS sorted CTL and CM CD33+CD14-HLA-DR+ cells did not significantly affect the proliferation of allogenic total T lymphocytes at 1:20 (p=0,54) or at 1:40 ratio (p=0,81). The CD33+CD14-HLA-DR+ PDL-1+ cells did not significantly modify allogenic T cells proliferation with respect to PDL- cells (p=0,11), while those cells which were CTLA4 negative caused a significant inhibition of T cell proliferation in comparison of CTLA4 positive cells (p=0,008). Conclusions: PaCa-derived soluble factors induce the expansion of the inhibitory lymphocytes subset CD4+CD25+ and a reduction of the immature CD33+CD14-DR+ dendritic cells. The tumor associated reduced expression of the inhibitory molecule CTLA4 in this cell population was demonstrated to characterize an immunosuppressive phenotype and this study suggests to take care in the use of anti-CTLA4 therapies

Pancreatic Tumors and Immature Immunosuppressive Myeloid Cells in Blood and Spleen: Role of Inhibitory Co-Stimulatory Molecules PDL1 and CTLA4. An In Vivo and In Vitro Study.

whether pancreatic adenocarcinoma (PDAC)-associated IMC subsets are induced by tumor-derived soluble factors and whether they are immunosuppressive focusing on the inhibitory co-stimulatory molecules PDL1 and CTLA4. S100A8/A9 complex, one of the possible inflammatory mediators of immune suppression in PDAC, induced PDL1 (p = 0.018) and reduced CTLA4 expression (p = 0.028) among IMCs. IMCs not expressing CTLA4 were demonstrated to be immune suppressive.In PDAC circulating dendritic and cytotoxic T cells are reduced, while MDSCs are increased and this might favour tumoral growth and progression. The reduced CTLA4 expression found among splenic IMCs of PDAC patients was demonstrated to characterize an immune suppressive phenotype and to be consequent to the direct exposure of myeloid cells to pancreatic cancer derived products, S100A8/A9 complex in particular