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Inorganic nanoparticles (NPs) represent promising examples of engineered nanomaterials, providing interesting biomedical solutions in several fields, like therapeutics and diagnostics. Despite the extensive number of investigations motivated by their remarkable potential for nanomedicinal applications, the interactions of NPs with biological interfaces are still poorly understood. The effect of NPs on living organisms is mediated by biological barriers, such as the cell plasma membrane, whose lateral heterogeneity is thought to play a prominent role in NPs adsorption and uptake pathways. In particular, biological membranes feature the presence of rafts, that is segregated lipid micro and/or nanodomains in the so-called liquid ordered phase (Lo ), immiscible with the surrounding liquid disordered phase (Ld ). Rafts are involved in various biological functions and act as sites for the selective adsorption of materials on the membrane. Indeed, the thickness mismatch present along their boundaries generates energetically favourable conditions for the adsorption of NPs. Despite its clear implications in NPs internalisation processes and cytotoxicity, a direct proof of the selective adsorption of NPs along the rafts' boundaries is still missing to date. Here we use multicomponent supported lipid bilayers (SLBs) as reliable synthetic models, reproducing the nanometric lateral heterogeneity of cell membranes. After being characterised by atomic force microscopy (AFM) and neutron reflectivity (NR), multidomain SLBs are challenged by prototypical inorganic nanoparticles, that is citrated gold nanoparticles (AuNPs), under simplified and highly controlled conditions. By exploiting AFM, we demonstrate that AuNPs preferentially target lipid phase boundaries as adsorption sites. The herein reported study consolidates and extends the fundamental knowledge on NPs-membrane interactions, which constitute a key aspect to consider when designing NPs-related biomedical applications. LAY DESCRIPTION: Inorganic nanoparticles (NPs) represent promising examples of engineered nanomaterials, offering interesting biomedical solutions in multiple fields like therapeutics and diagnostics. Despite being extensively investigated due to their remarkable potential for nanomedicinal applications, the interaction of NPs with biological systems is in several cases still poorly understood. The interaction of NPs with living organisms is mediated by biological barriers, such as the cell plasma membrane. Supported lipid bilayers (SLBs) represent suitable synthetic membrane models for studying the physicochemical properties of natural interfaces and their interaction with inorganic nanomaterials under simplified and controlled conditions. Recently, multicomponent SLBs were developed in order to mimic the lateral heterogeneity of most biological membranes. In particular, biological membranes feature the presence of rafts, that is segregated lipid micro and/or nanodomains, enriched in cholesterol, sphingomyelin, saturated glycerophospholipids and glycosphingolipids: these lipids segregate in the so-called liquid-ordered phase (Lo ), characterised by a high molecular packing degree, which promotes the phase separation from the surrounding liquid-crystalline (disordered, Ld ) phase, where the intermolecular mobility is increased. Rafts are thought to participate in the formation and targeting of nano-sized biogenic lipid vesicles and are also actively involved in multiple membrane processes. Indeed, Lo -Ld phase boundaries represent high energy areas, providing active sites for the preferential adsorption of external material. The selective adsorption of NPs along the phase boundaries of rafted membranes has been theorised and indirectly probed by different research groups; however, a direct proof of this phenomenon is still missing to date. We herein exploit atomic force microscopy (AFM) to directly visualise the preferential adsorption of gold nanoparticles (AuNPs) along the phase boundaries of multicomponent SLBs (previously characterised by neutron reflectivity), obtained from synthetic vesicles containing both an Ld and an Lo phase. The quantitative localisation and morphometry of AuNPs adsorbed on the SLB reveal important information on their interaction with the lipid matrix and directly prove the already theorised differential NPs-lipid interaction at the phase boundaries. The presented results could help the development of future NP-based applications, involving NPs adsorption on membranes with nanoscale phase segregations.

Hybrid Magnetite-gold type nanoparticles with core-shell structure coated by a further outer layer of phospholipids including ruthenium complexes with antitumor activity and peptide sequences, the process 5 for their preparation and their use for simultaneous use as contrast agents for magnetic resonance imaging and as antitumor agents are disclosed

La presente invenzione si riferisce al settore delle nanoparticelle e più in particolare a delle nanoparticelle ibride del tipo magnetite-oro con struttura nucleo-guscio (core-shell) funzionalizzate con uno strato esterno di fosfolipidi comprendente ulteriormente complessi di rutenio ad attività antitumorale ed eventualmente sequenze peptidiche, il procedimento per la loro preparazione ed il loro uso per l???impiego simultaneo come agenti di contrasto per le tecniche di diagnostica per immagini e come agenti antitumorali.

The aggregation behavior of a novel class of amphiphilic RGD integrin binders is studied

Lipopolysaccharides (LPSs) are amphiphilic macromolecules indispensable for the growth and the survival of Gram-negative bacteria, one of the most diffuse classes of pathogenic bacteria. LPS are composed of a hydrophilic heteropolysaccharide unit, covalently linked to a lipophilic moiety called lipid A, which is embedded in the outer leaflet and anchors these macromolecules to the lipid membrane. Recent studies have revealed that presumably the physical characteristics of these molecules are correlated to their biological activity.Here we present an investigation with a twofold goal. First, we try to connect LPS aggregation behavior to their molecular structure. Second, we attempt to investigate on a possible interaction mechanism between LPS model membranes and hybrid antimicrobial peptides used in the cystic fibrosis therapy treatment.All the investigations have been performed using an experimental strategy which has been proved to be extremely informative, combining dynamic light scattering (DLS) to estimate liposome dimension, small angle neutron scattering (SANS) to analyze the aggregate morphology and for estimating the thickness of the lipid bilayer and electron paramagnetic resonance spectroscopy (EPR) to investigate the dynamics of the lipids in the bilayer. These techniques have also been useful to give insights on the effect of antimicrobial peptides on the lipid bilayer.

Dissolution of surfactants into bilayer lipid membranes results in their destabilization so that, as a final result, mixed micelles containing both polar lipids and surfactants molecules are formed. It is to note that eventual transient aggregates, formed during the process, could be multilamellar vesicles. The equilibrium and the transient structures occurred in the transition, as well as kinetic of dissolution of the surfactant in the bilayer membrane are very important issues for the study of the stability of liposomes used in medical therapy and for the study of the interaction between detergent and living cells. In previous studies Almagren has related the structures and the equilibrium properties encountered in the transition to the phase behavior. However in his studies the kinetic of the process and details on the structural properties of the transient aggregates are missing. In this poster, we present a study on the dissolution kinetics of DOPC phospholipids due to presence of C10E8 surfactant molecules, at different concentrations at 25°C. Structural characterization performed by means of small angle neutron scattering and Electron Spin Resonance Spectroscopy allowed establishing a different behavior dependent on the surfactant amount. When the C10E8 concentration is below its cmc values, the DOPC unilamellar liposomes are progressively transformed in mixed giant multilamellar vesicles as shown by SANS measurements: the transition occurs in ~ 2 weeks after the insertion of the surfactant. When the C10E8 concentration is well above its cmc the liposome rupture is much faster (less than 12 hours) and results in the formation of small mixed micelles formed by the two solutes.

Metastases rather than primary tumors are the leading cause for cancer death, and yet metastases are almost never the target of chemotherapy. At present, Ruthenium complexes have been found to offer new perspectives. Although a rather large number of studies on Ruthenium complexes have been published in the recent years, up to date in literature no examples of nanovectors carrying Ruhenium complexes for anticancer therapy are reported. At this aim, we have synthesized a new amphiphilic unimer able to coordinate Ruthenium complexes and to form liposomes. This unimer (DOPU) has been obtained from an uridine derivative by traightforward introduction of a pyridine function on the uracile base. The hydrophobic part of the molecule consists of a double C18 oleoyl chain. The ligand unimer DOPU has been afterward coordinated to Ru(III). Preliminary SANS, Cryo-TEM and DLS measurements have confirmed the presence of unilamellar and oligolamellar liposomes, as well as the existence of more complex structures like cubosomes. The findings in the present study open up new vistas for the application of lipid based supramolecular systems in Ruthenium anti-cancer therapy. The lodgment of Ruthenium complexes in amphiphilic nanovectors allows a higher amount of drug in the bloodstream compared to the case when it is administrated as a free complex. Furthermore, amphiphilic nanovectors are able to protect the Ruthenium complexes from enzymatic and/or environmental degradation that could otherwise occur during bloodstream circulation.