Universality of DNA Adsorption Behavior on the Cationic Membranes of Nanolipoplexes.

Nanolipoplexes have emerged worldwide as the most pRev.alent synthetic gene delivery system. Nowadays, it is accepted that complete DNA protection and a precise control of the physical attributes of emerging complexes are major steps toward rational design of efficient nanocarriers. Here we Rev.ise the mechanism of DNA adsorption to the cationic membranes of lipid nanovectors. Here we show that both the DNA-binding ability of cationic membranes and the one-dimensional DNA packing density inside the complex depen on the cationic lipid/anionic DNA charge ratio. Remarkably, both these distributions are rescaled on universal curves when plotted against γ, a dimensionless quantity expressing the ratio between the area of cationic membranes and that occupied by DNA molecules. As a result, the DNA condensation on the surface of lipid nanocarriers can be regarded as a two-step process. Our findings indicate a successful way to the rational design of next-generation drug delivery nanocarriers

Author Correction: Salt concentration and charging velocity determine ion charge storage mechanism in nanoporous supercapacitors

Correction to: Nature Communications; https://doi.org/10.1038/s41467-018-06612-4; published online 08 October 2018 The original version of this Article contained an error in the Acknowledgements, which was incorrectly omitted from the end of the following: ‘The research leading to these results has received funding from the European Community’s Horizon 2020 Framework Programme under grant agreement nº 730872.’ This has been corrected in both the PDF and HTML versions of the Article

Snapshots into carbon dots formation through a combined spectroscopic approach

The design of novel carbon dots with ad hoc properties requires a comprehensive understanding of their formation mechanism, which is a complex task considering the number of variables involved, such as reaction time, structure of precursors or synthetic protocol employed. Herein, we systematically investigated the formation of carbon nanodots by tracking structural, chemical and photophysical features during the hydrothermal synthesis. We demonstrate that the formation of carbon nanodots consists of 4 consecutive steps: (i) aggregation of small organic molecules, (ii) formation of a dense core with an extended shell, (iii) collapse of the shell and (iv) aromatization of the core. In addition, we provide examples of routes towards tuning the core-shell design, synthesizing five novel carbon dots that all consist of an electron-dense core covered by an amine rich ligand shell

Capabilities of a novel electrochemical cell for operando XAS and SAXS investigations for PEM fuel cells and water electrolysers

Catalyst stability is a key issue in current electrochemical devices, such as fuel cells (FCs) and water electrolysers (WEs). While for FCs, the main degradation process limiting catalyst stability have been highlighted, a clear picture is still missing concerning WEs. In this framework, in operando analyses are essential to characterize catalyst degradation over time. As X-Rays constitute the perfect probe for studying catalytic materials, we here present a reversible electrochemical cell designed for operando X-Ray Absorption Spectroscopy and Small and Wide Angle X-Ray Scattering analyses, which was used: (i) to study Pt/C catalyst degradation coupling the evolution of specific electrochemically active surface area (ECSA) with catalyst morphology, supported by the analysis of Pt oxidation state. As a result, an increase of particle (and particle cluster) size is connected to the diminishing of ECSA and to the changes in the fraction of metallic-to-oxidised Pt, underlying that changes mainly develop in the first 2000 cycles of applied stress tests. Finally, (ii) we introduce some preliminary results underlying the change in Ir oxidation state for a standard Ir/IrOX catalyst material for WEs, showing as such a change is not sufficient to induce any remarkable morphological variations within 500 cycles of stress tests

DNA release from cationic liposome/DNA complexes by anionic lipids

The authors found that recently developed multicomponent cationic liposome DNA complexes (lipoplexes) exhibit higher transfection efficiency with respect to usually employed binary lipoplexes in NIH 3T3 and A17 cell lines. Interaction of lipoplexes with anionic liposomes (model of cellular membranes) was investigated by synchrotron small angle x-ray diffraction. The authors used one-dimensional DNA packing density to estimate the molar fraction of DNA released from lipoplexes by anionic lipids

Enhanced transfection efficiency of multicomponent lipoplexes in the regime of optimal membrane charge density

Recently, membrane charge density of lipid membranes, am, has been recognized as a universal parameter that controls the transfection efficiency of complexes made of binary cationic liposomes and DNA (binary lipoplexes). Three distinct regimes, most likely related to interactions between complexes and cells, have also been identified. The purpose of this work was to investigate the transfection efficiency behavior of multicomponent lipoplexes in the regime of optimal membrane charge density (1 < sigma(M) < 2 x 10(-2) e/angstrom(2)) and compare their performance with that of binary lipoplexes usually employed for gene delivery purposes. We found remarkable differences in transfection efficiency due to lipid composition, with maximum in efficiency being obtained when multicomponent lipoplexes were used to transfect NIH 3T3 cells. while binary lipoplexes were definitely less efficient. These findings suggested that multicomponent systems are especially promising lipoplex candidates. With the aim of providing new insights into the mechanism of transfection, we investigated the structural evolution of lipoplexes when interacting with anionic (cellular) lipids by means of synchrotron small-angle X-ray diffraction (SAXD), while the extent of DNA release upon interaction with anionic lipids was measured by electrophoresis on agarose gels. Interestingly, a clear trend was found that the transfection activity increased with the number of lipid components. These results highlight the compositional properties of carrier lipid/cellular lipid mixtures as decisive factors for transfection and suggest a strategy for the rational design of superior cationic lipid carriers

Structural stability against disintegration by anionic lipids rationalizes the efficency of cationic liposom/DNA complexes

Reported here is the correlation between the transfection efficiency of cationic liposome/DNA complexes (lipoplexes) and the structural evolution that they undergo when interacting with anionic membrane lipids. Multicomponent lipoplexes, incorporating from three to six lipid species simultaneously, presented a much higher transfection efficiency than binary lipoplexes, which are more commonly used for gene-delivery purposes. The discovery that a high transfection efficiency can be achieved by employing multicomponent complexes at a lower-than-ever-before membrane charge density of lipoplexes was of primary significance. Synchrotron small-angle X-ray diffraction (SAXD) experiments showed that anionic liposomes made of dioleoylphosphatidylglycerol (DOPG) disintegrated the lamellar phase of lipoplexes. DNA unbinding was measured by electrophoresis on agarose gels. Most importantly, structural changes induced by anionic lipids strictly depended on the lipid composition of lipoplexes. We found evidence of the existence of three different regimes of stability related to the interaction between complexes and anionic membranes. Both unstable (with low membrane charge density, !M) andhighly stable lipoplexes (withhigh !M) exhibited lowtransfection efficiency whereas highly efficient multicomponent lipoplexes exhibited an “optimal stability”. This intermediate regime reflects a compromise between two opposing constraints: protection of DNA in the cytosol and endosomal escape. Here we advance the concept that structural stability, upon interaction with cellular anionic lipids, is a key factor governing the transfection efficiency of lipoplexes. Possible molecular mechanisms underlying experimental observations are also discussed