Franco Fileni

Documento che racconta il rapporto umano e la stima professionale da parte del Magnifico Rettore dell'Università degli Studi di Trieste, attualmente in carica, nei confronti del collega scomparso

Perceptions and Misconceptions in Molecular Recognition: Key Factors in Self-Assembling Multivalent (SAMul) Ligands/Polyanions Selectivity

Biology is dominated by polyanions (cell membranes, nucleic acids, and polysaccharides just to name a few), and achieving selective recognition between biological polyanions and synthetic systems currently constitutes a major challenge in many biomedical applications, nanovectors-assisted gene delivery being a prime example. This review work summarizes some of our recent efforts in this field; in particular, by using a combined experimental/computation approach, we investigated in detail some critical aspects in self-assembled nanomicelles and two major polyanions-DNA and heparin

Evolution from Covalent to Self-Assembled PAMAM-Based Dendrimers as Nanovectors for siRNA Delivery in Cancer by Coupled In Silico-Experimental Studies. Part I: Covalent siRNA Nanocarriers

Small interfering RNAs (siRNAs) represent a new approach towards the inhibition of gene expression; as such, they have rapidly emerged as promising therapeutics for a plethora of important human pathologies including cancer, cardiovascular diseases, and other disorders of a genetic etiology. However, the clinical translation of RNA interference (RNAi) requires safe and efficient vectors for siRNA delivery into cells. Dendrimers are attractive nanovectors to serve this purpose, as they present a unique, well-defined architecture and exhibit cooperative and multivalent effects at the nanoscale. This short review presents a brief introduction to RNAi-based therapeutics, the advantages offered by dendrimers as siRNA nanocarriers, and the remarkable results we achieved with bio-inspired, structurally flexible covalent dendrimers. In the companion paper, we next report our recent efforts in designing, characterizing and testing a series of self-assembled amphiphilic dendrimers and their related structural alterations to achieve unprecedented efficient siRNA delivery both in vitro and in vivo

Evolution from Covalent to Self-Assembled PAMAM-Based Dendrimers as Nanovectors for siRNA Delivery in Cancer by Coupled in Silico-Experimental Studies. Part II: Self-Assembled siRNA Nanocarriers

In part I of this review, the authors showed how poly(amidoamine) (PAMAM)-based dendrimers can be considered as promising delivering platforms for siRNA therapeutics. This is by virtue of their precise and unique multivalent molecular architecture, characterized by uniform branching units and a plethora of surface groups amenable to effective siRNA binding and delivery to e.g., cancer cells. However, the successful clinical translation of dendrimer-based nanovectors requires considerable amounts of good manufacturing practice (GMP) compounds in order to conform to the guidelines recommended by the relevant authorizing agencies. Large-scale GMP-standard high-generation dendrimer production is technically very challenging. Therefore, in this second part of the review, the authors present the development of PAMAM-based amphiphilic dendrons, that are able to auto-organize themselves into nanosized micelles which ultimately outperform their covalent dendrimer counterparts in in vitro and in vivo gene silencing

Sustainability Analysis of Hydrogen Production Processes: a Comparison Based on Sustainability Indicators

Hydrogen is a versatile energy carrier and storage medium that may be employed in a variety of applications. It may be produced using different processes. In this work, process simulation is used to obtain material and energy balances for each process investigated, as well as for the evaluation of capital and maintenance costs. Process simulation outcomes are then used to estimate three key performance indicators focusing on sustainability issues: the energy return of energy invested, the levelized cost of hydrogen and the life cycle assessment. We compared several hydrogen generation processes, each denoted by a unique colour code: (i) green hydrogen, produced by electrolysis of water using electricity from renewable sources, (ii) grid hydrogen, produced by electrolysis using grid electricity, (iii) grey hydrogen, produced from natural gas using steam reforming and (iv) blue hydrogen, like grey one, but coupled with carbon capture and storage. In conclusion, the most sustainable hydrogen production method is the green hydrogen, produced by water electrolysis

Highly grafted polystyrene/polyvinylpyridine polymer gold nanoparticles in a good solvent: effects of chain length and composition

In this work, the structural features of spherical gold nanoparticles (NPs) decorated with highly grafted poly(styrene) (PS), poly(vinylpyridine) (PVP) and PS\u2013PVP diblock copolymer brushes immersed in a good solvent are investigated by means of Dissipative Particle Dynamics (DPD) simulations as a function of grafted chain length and of homopolymer and copolymer chain composition. For NPs grafted either by PS or PVP homopolymer brushes (selected as a proof of concept), good agreement between the Daoud\u2013Cotton theory, experimental evidence, and our DPD simulations is observed in the scaling behavior of single chain properties, especially for longer grafted chains, and in brush thickness prediction. On the other hand, for grafted chain lengths comparable to NP dimensions parabolic-like profiles of the end-monomer distributions are obtained. Furthermore, a region of high concentration of polymer segments is observed in the monomer density distribution for long homopolymers. In the case of copolymer-decorated NPs, the repulsion between PS and PVP blocks is found to substantially influence the radius of gyration and the shape of the end-monomer distribution of the relevant polymer shell. Moreover, for diblock chains, the un-swollen region is observed to be thinner (and, correspondingly, the swollen layer thicker) than that of a NP modified with a homopolymer of the same length. Finally, the lateral segregation of PS and PVP blocks is evidenced by our calculations and a detailed analysis of the corona behavior is reported, thus revealing the key parameters in controlling the surface properties and the response of diblock copolymer modified nanoparticles

Computer-assisted design, synthesis, binding and cytotoxicity assessments of new 1-(4-(aryl(methyl)amino)butyl)-heterocyclic sigma 1 ligands

In this work we applied a blend of computational and synthetic techniques with the aim to design, synthesize, and characterize new \u3c31 receptor (\u3c31R) ligands. Starting from the structure of previously reported, high-affinity benzoxazolone-based \u3c31 ligands, the threedimensional homology model of the \u3c31R was exploited for retrieving the molecular determinants to fulfill the optimal pharmacophore requirements. Accordingly, the benzoxazolone moiety was replaced by other heterocyclic scaffolds, the relevant conformational space in the \u3c31R binding cavity was explored, and the effect on \u3c31R binding affinity was ultimately assessed. Next, the compounds designed in silico were synthesized, and their affinity and selectivity toward \u3c31 and \u3c32 receptors were tested. Finally, a representative series of best \u3c31R binders were assayed for cytotoxic activity on the SH-SY5Y human neuroblastoma cell line. Specifically, the new 4-phenyloxazolidin-2-one derivatives 2b (i.e., (R)-2b and (S)-2b) emerged as potential leads for further development as \u3c31R agents, as they were found endowed with the highest \u3c31R affinity (Ki\u3c31 values in the range 0.95-9.3 nM), and showed minimal cytotoxic levels exhibited in the selected, cell-based test, in line with a \u3c31R agonist behavior