NANOBIOINTERACTIONS: CHEMOKINE MEDIATED SELECTIVE TARGETING OF NANOPARTICLES

A major challenge in nanomedicine is the preparation of nano-tools with the ability to selectively targeting diseased tissues. Functionalization of nanoparticles (NPs) by conjugation with specific ligands possessing the inherent ability to bind only cell subsets confer \u201csmartness\u201d to NPs. Due to their small sizes, nanostructures exhibit unique physicochemical and biological properties, such as enhanced reactive area as and the ability to cross tissue barriers, making them a favorable material for biomedical applications. NPs vary in size ranging from 5 to 500 nm. Through the manipulation of size, surface chemistry and material structure, NPs can be tailored to carry therapeutic or imaging agents for delivery to specific tissues. In particular, surface functionalization can modify NP interaction with the immune system cells and the acquisition of stealth or specific-targeting properties. NP surface decoration with peptide moieties is one of the most efficacious cell-targeting strategies. In the first part of my PhD project, I focused on NP surface functionalization with stable proteins that interact with different immune cells in a selective manner. I used chemokines (chemo-attractant cyto-kines) due to their role in physiological and pathological binding and regulation of immune cells, as well as their structural stability in biological media. I modified a prototype SiO2-NP surface with the chemokine CXCL5, adsorbed or covalently bound, to precisely targeting CXCR2+ immune cells. The development of CXCL5-NPs and the discovery of their targeting properties provide novel results. Specifically, these protein-decorated nano-tools showed enhanced uptake and precise receptor-mediated cell subset localization. Moreover, given the crucial role of CXCR2 in inflammatory responses and cancer biology, CXCL5-NPs pave the way to prepare new delivery systems with increased capabilities and potential modulation of immune responses. In the second part of my PhD project, I evaluated the effects of PtNPs on HL60 and differentiated HL60 cells in immune responses and inflammatory diseases. Reactive Oxygen Species (ROS) removing activity within cells is often achieved with different catalytic nanomaterials. Among them, PtNPs attract great attention due to their efficient catalysis and good degree of cyto-compatibility, but information about their effects on the human immune system is still missing. Further investigation using undifferentiated and differentiated neutrophil-like HL60 confirmed the harmlessness and non-cytotoxicity of PtNPs with non-adherent innate immune cells, contributing to the knowledge of PtNP interaction with immune cells in view of their potential applications in nanomedicine

Quale software didattico per il bambino sordo?

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Evolutionary history of the ADRB2 gene in humans

No abstract available

RpL3 promotes the apoptosis of p53 mutated lung cancer cells by down-regulating CBS and NFκB upon 5-FU treatment

5-FU is a chemotherapy drug commonly used for the treatment of human cancers; however drug resistance represents a major challenge for its clinical application. In the present study, we reporte that rpL3 induced by 5-FU treatment in Calu-6 cells represses CBS transcription and reduces CBS protein stability leading to a decrease of CBS protein levels. rpL3 also regulates negatively the activation of NFκB by preventing NFκB nuclear translocation through IκB-α up-regulation. Furthermore, we demonstrate that rpL3 significantly enhances the apoptosis of 5-FU treated Calu-6 cells promoting the overexpression of the pro-apoptotic proteins Bax and the inhibition of the anti-apoptotic protein Bcl-2. We finally demonstrate that rpL3 potentiates 5-FU efficacy inhibiting cell migration and invasion. Our results suggest that combination of rpL3 and 5-FU is a promising strategy for chemotherapy of lung cancers lacking functional p53 that are resistant to 5-FU