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The ability to control the properties of monolayer protected gold nanoparticles (MPNPs) discloses unrevealed features stemming from collective properties of the ligands forming the ...monolayer and presents opportunities to design new materials. To date, the influence of ligand end-group size and capacity to form hydrogen bonds on structure and hydration of small MPNPs (<5 nm) has been poorly studied. Here, we show that both features determine ligands order, solvent accessibility, capacity to host hydrophobic compounds and interfacial properties of MPNPs. The polarity perceived by a radical probe and its binding constant with the monolayer investigated by electron spin resonance is rationalized by molecular dynamics simulations, which suggest that larger space-filling groups – trimethylammonium, zwitterionic and short polyethylene glycol – favor a radial organization of the thiolates, whereas smaller groups – as sulfonate – promote the formation of bundles. Zwitterionic ligands create a surface network of hydrogen bonds, which affects nanoparticle hydrophobicity and maximize the partition equilibrium constant of the probe. This study discloses the role of the chemistry of the end-group on monolayer features with effects that span from molecular- to nano-scale and opens the door to a shift in the conception of new MPNPs exploiting the end-group as a novel design motif.
A hierarchical procedure bridging the gap between atomistic and mesoscopic simulation for polymer−clay nanocomposite (PCN) design is presented. The dissipative particle dynamics (DPD) is adopted as ...the mesoscopic simulation technique, and the interaction parameters of the mesoscopic model are estimated by mapping the corresponding energy values obtained from atomistic molecular dynamics (MD) simulations. The predicted structure of the nylon 6 PCN system considered is in excellent agreement with previous experimental and atomistic simulation results.
Gene therapy has recently reached the front line in the treatments of different diseases. Although graphene oxide has been widely used as a gene vector, its clinical application is limited by the ...scarce inhomogeneity of the different synthetic methods. Recently, we have developed the preparation of a new class of graphene oxide, named oxo-G, obtained by a rigorous synthetic method with controlled size and surface chemistry. oxo-G has been successfully applied for the production of reduced graphene oxide with remarkable conductivity. Here, we applied oxo-G to gene delivery. After ad hoc functionalization, we found that oxo-G is able to efficiently complex siRNA and strongly induce gene silencing in vitro at five pg/cell doses, more than 20 times lower than the best results reported in the literature using graphene-based materials. The aim of this work is to inspire the readers to develop further oxo-G materials for biomedical applications. We hope that oxo-G can be considered as an alternative candidate in future gene silencing use in vivo.
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Liquid‐phase exfoliation (LPE) in aqueous solutions provides a simple, scalable, and green approach to produce 2D materials. By combining atomistic simulations with exfoliation experiments, the ...interaction between a surfactant and a 2D layer at the molecular scale can be better understood. In this work, two different dyes, corresponding to rhodamine B base (Rbb) and to a phenylboronic acid BODIPY (PBA‐BODIPY) derivative, are employed as dispersants to exfoliate graphene and hexagonal boron nitride (hBN) through sonication‐assisted LPE. The exfoliated 2D sheets, mostly as few‐layers, exhibit good quality and high loading of dyes. Using molecular dynamics (MD) simulations, the binding free energies are calculated and the arrangement of both dyes on the layers are predicted. It has been found that the dyes show a higher affinity toward hBN than graphene, which is consistent with the higher yields of exfoliated hBN. Furthermore, it is demonstrated that the adsorption behavior of Rbb molecules on graphene and hBN is quite different compared to PBA‐BODIPY.
Liquid‐phase exfoliation is a powerful methodology to produce 2D materials. The use of rhodamine B base and PBA‐BODIPY dispersants has allowed generating few‐layer graphene and hexagonal boron nitride (hBN) through a sonication‐assisted exfoliation. The exfoliated graphene and hBN with a high loading of dispersants exhibit good dispersibility and low defect content. Moreover, atomistic simulations are exploited to understand the interaction between the nanosheets and the two dispersant molecules.
The development of efficient and safe nucleic acid delivery vectors remains an unmet need holding back translation of gene therapy approaches to the bedside. Graphene oxide (GO) could help bypass ...such bottlenecks, thanks to its large surface area, versatile chemistry and biocompatibility, which could overall enhance transfection efficiency while abolishing some of the limitations linked to the use of viral vectors. Here, we aimed to assess the capacity of bare GO, without any further surface modification, to complex a short double-stranded nucleic acid of biological relevance (siRNA) and mediate its intracellular delivery. GO formed stable complexes with siRNA at 10 : 1, 20 : 1 and 50 : 1 GO : siRNA mass ratios. Complexation was further corroborated by atomistic molecular dynamics simulations. GO : siRNA complexes were promptly internalized in a primary mouse cell culture, as early as 4 h after exposure. At this time point, intracellular siRNA levels were comparable to those provided by a lipid-based transfection reagent that achieved significant gene silencing. The time-lapse tracking of internalized GO and siRNA evidenced a sharp decrease of intracellular siRNA from 4 to 12 h, while GO was sequestered in large vesicles, which may explain the lack of biological effects (i.e. gene silencing) achieved by GO : siRNA complexes. This study underlines the potential of non-surface modified GO flakes to act as 2D siRNA delivery platforms, without the need for cationic functionalization, but warrants further vector optimization to allow the effective release of the nucleic acid and achieve efficient gene silencing.
The structures and physicochemical properties of surface-stabilizing molecules play a critical role in defining the properties, interactions, and functionality of hybrid nanomaterials such as ...monolayer-stabilized nanoparticles. Concurrently, the distinct surface-bound interfacial environment imposes very specific conditions on molecular reactivity and behavior in this setting. Our ability to probe hybrid nanoscale systems experimentally remains limited, yet understanding the consequences of surface confinement on molecular reactivity is crucial for enabling predictive nanoparticle synthon approaches for postsynthesis engineering of nanoparticle surface chemistry and construction of devices and materials from nanoparticle components. Here, we have undertaken an integrated experimental and computational study of the reaction kinetics for nanoparticle-bound hydrazones, which provide a prototypical platform for understanding chemical reactivity in a nanoconfined setting. Systematic variation of just one molecular-scale structural parameterthe distance between reactive site and nanoparticle surfaceshowed that the surface-bound reactivity is influenced by multiscale effects. Nanoparticle-bound reactions were tracked in situ using 19F NMR spectroscopy, allowing direct comparison to the reactions of analogous substrates in bulk solution. The surface-confined reactions proceed more slowly than their solution-phase counterparts, and kinetic inhibition becomes more significant for reactive sites positioned closer to the nanoparticle surface. Molecular dynamics simulations allowed us to identify distinct supramolecular architectures and unexpected dynamic features of the surface-bound molecules that underpin the experimentally observed trends in reactivity. This study allows us to draw general conclusions regarding interlinked structural and dynamical features across several length scales that influence interfacial reactivity in monolayer-confined environments.
This paper reports a small family of cationic surfactants designed to bind polyanions such as DNA and heparin. Each molecule has the same hydrophilic cationic ligand and a hydrophobic aliphatic group ...with eighteen carbon atoms with one, two, or three alkene groups within the hydrophobic chain (C18‐1, C18‐2 and C18‐3). Dynamic light scattering indicates that more alkenes lead to geometric distortion, giving rise to larger self‐assembled multivalent (SAMul) nanostructures. Mallard Blue and Ethidium Bromide dye displacement assays demonstrate that heparin and DNA have markedly different binding preferences, with heparin binding most effectively to C18‐1, and DNA to C18‐3, even though the molecular structural differences of these SAMul systems are buried in the hydrophobic core. Multiscale modelling suggests that adaptive heparin maximises enthalpically favourable interactions with C18‐1, while shape‐persistent DNA forms a similar number of interactions with each ligand display, but with slightly less entropic cost for binding to C18‐3—fundamental thermodynamic differences in SAMul binding of heparin or DNA. This study therefore provides unique insight into electrostatic molecular recognition between highly charged nanoscale surfaces in biologically relevant systems.
The inside controls the outside: Structural changes to the hydrophobic units direct self‐assembly and control the display of cationic ligands on the surface of SAMul nanostructures—DNA and heparin then show different binding preferences to the surface ligands.
Organic–inorganic (O–I) nanomaterials are versatile platforms for an incredible high number of applications, ranging from heterogeneous catalysis to molecular sensing, cell targeting, imaging, and ...cancer diagnosis and therapy, just to name a few. Much of their potential stems from the unique control of organic environments around inorganic sites within a single O–I nanomaterial, which allows for new properties that were inaccessible using purely organic or inorganic materials. Structural and mechanistic characterization plays a key role in understanding and rationally designing such hybrid nanoconstructs. Here, we introduce a general methodology to identify and classify local (supra)molecular environments in an archetypal class of O–I nanomaterials, i.e., self-assembled monolayer-protected gold nanoparticles (SAM-AuNPs). By using an atomistic machine-learning guided workflow based on the Smooth Overlap of Atomic Positions (SOAP) descriptor, we analyze a collection of chemically different SAM-AuNPs and detect and compare local environments in a way that is agnostic and automated, i.e., with no need of a priori information and minimal user intervention. In addition, the computational results coupled with experimental electron spin resonance measurements prove that is possible to have more than one local environment inside SAMs, being the thickness of the organic shell and solvation primary factors in the determining number and nature of multiple coexisting environments. These indications are extended to complex mixed hydrophilic–hydrophobic SAMs. This work demonstrates that it is possible to spot and compare local molecular environments in SAM-AuNPs exploiting atomistic machine-learning approaches, establishes ground rules to control them, and holds the potential for the rational design of O–I nanomaterials instructed from data.
The aberrant misfolding and aggregation of alpha synuclein (αS) into toxic oligomeric species is one of the key features associated with the pathogenesis of Parkinson's disease (PD). It involves ...different biochemical and biophysical factors as plasma membrane binding and interaction with heavy metal ions. In the present work, atomic force microscopy (AFM) is combined with Fourier Transform Infrared Spectroscopy (FTIR) measurements to investigate the interaction of wild-type (WT) and A53T mutated alpha synuclein with artificial lipid bilayers mimicking lipid raft (LR) domains, before and after ferrous cations (Fe
) treatment. In the absence of iron, protein monomers produce a thinning of the membrane, targeting the non-raft phase of the bilayer preferentially. On the contrary, iron actively promotes the formation of globular protein aggregates, resembling oligomers, targeted to LR domains. In both aggregation states, monomer and oligomer, the mutated A53T protein exhibits a greater and faster membrane-interaction. These results underlie a new mechanism of membrane-protein interaction in PD. The targeting of Fe
-promoted αS oligomers to LRs might be functional for the disease and be helpful for the development of new therapeutic strategies.
Low-generation viologen-phosphorous dendrimers (VPDs) can be exploited as novel therapeutic agents, since they efficiently inhibit aggregation of amyloid-β into fibrils and are active against several ...strains of microorganisms. Human serum albumin (HSA), the most abundant plasma protein, is playing an increasing role as drug carrier in the clinical setting. Therefore, with the aim of exploiting HSA as a potential carrier for VPDs, in this work we performed a preliminary investigation of the interaction of six different VPDs 1–6 with HSA using a combined computational/experimental approach. First, different modeling techniques were employed to i) determine the dendrimer binding site on the HSA surface; ii) derive the free energy change ΔGb involved in each dendrimer/HSA complex formation; iii) analyze in details all molecular determinants contributing to ΔGb, and iv) evaluate the eventual HSA structural variations induced by dendrimer binding. All modeling predictions were next validated using a series of experimental techniques, including isothermal titration calorimetry (ITC), circular dichroism (CD), and fluorescence quenching and decay. In aggregate, the results from this study allowed us to rank the affinity of the different viologen-phosphorous dendrimers 1–6 towards HSA and to formulate a molecular-based rationale for the differential binding thermodynamics of the resulting dendrimer/HSA complexes. According to our data, HSA can successfully and selectively bind VPDs 1–6, dendrimer 4 being the best cargo for this endogenous protein nanocarrier.
•Human serum albumin (HSA) is a powerful, natural drug carrier.•Viologen-phosphorous dendrimers (VDPs) are highly efficient therapeutic agents.•We studied VDP/HSA binding thermodynamics by computational/experimental techniques.•HSA can be successfully exploited as an endogenous receptor for VDPs.
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