Graphene oxide affects in vitro fertilization outcome by interacting with sperm membrane in an animal model

We realized the exposure of boar spermatozoa to graphene oxide (GO) at concentration of 0.5, 1, 5, 10 and 50 μg/mL in an in vitro system able to promote the capacitation, i.e. the process that allows sperm cells to became fertile. Interestingly, we found that the highest GO concentration (5, 10 and 50 μg/mL) are toxic for spermatozoa, while the lowest ones (0.5 and 1 μg/mL) seem to significantly increase the sperm cells fertilizing ability (p >.05) in an in vitro fertilization experiment. To explain this finding, we investigated the effect of GO on sperm membrane structure (atomic force microscopy) and function (confocal microscopy and flow cytometry, substrate adhesion). As a result, we found that GO is able to interact with spermatozoa membranes and, in particular, it seems to be able to extract the cholesterol, which is a key player in spermatozoa physiology, from plasma membrane of boar spermatozoa incubated under capacitation conditions. In our opinion, these results are very important because they allow identifying either a plausible mechanism of GO toxicity on spermatozoa and new strategies to manage sperm capacitation

Liposome-induced exfoliation of graphite to few-layer graphene dispersion with antibacterial activity

Liposome-induced exfoliation of graphite allowed to obtain few-layer graphene homogeneous in size and hydrophilic due to the non-covalent functionalization with phospholipids. The corresponding dispersions are stable for 48 h and demonstrate antimicrobial activity

Incorporation of Calix[6]Arene Macrocycles and (Pseudo)Rotaxanes in Bilayer Membranes: Towards Controllable Artificial Liposomal Channels

The growing interest in the study of membrane-active ion (in particular, anion) transporters motivates the investigation of the mechanisms that underlie the transport process. The interest of the scientific community in this area is largely due to the great importance of transmembrane ion-transport phenomena in many diseases. In this paper we investigated the role of calix[6]arene-based pseudorotaxanes and rotaxanes on transmembrane transport of ions across the bilayer of liposomes composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC; diameter 100 nm). We evaluated the effect of these interlocked systems on the properties of the bilayer and on membrane permeability towards chloride ions and 5(6)-carboxyfluorescein. These findings may pave the way for the construction of new generations of pharmacological systems regulating the transport of chloride ions

Light-driven directed proton transport across the liposomal membrane

We have developed a simple artificial photoresponsive ion-gating device by inserting molecular switches in the membrane of liposomes. A controlled and directed proton transport across the bilayer membrane can lower the internal pH of the liposomes from neutral to around 4 under combined light and chemical stimulation

Elucidating chemical reactivity and transition state of mononuclear rearrangement of heterocycles through the use o fcompartimentalized micellar media

The present comprehensive kinetic investigation in micellar systems deepens and broadens theknowledge of mononuclear rearrangement of heterocycles (MRH) of Z-phenylhydrazone of 3-benzoyl-5-phenyl-1,2,4-oxadiazole, reaction already carried out in different reaction media. As a matter of factthe use of four types of micelles different for charge, shape and polarity has allowed us to evaluate therole of micellar systems, as reaction media, on the rate of MRH and to quantify their catalytic effect.Moreover, the data obtained have enabled us to draw some intriguing conclusions on the localization ofthe substrate in the micelles, the transition state structure and the driving force of the reaction

Ionic Liquids as "Masking" solvents of the relative strength of bases in proton transfer reactions

Equilibrium constants for the proton transfer reaction between pyridines and trifluoroacetic acid were measured in room-temperature ionic liquids (ILs) of different cation–anion compositions. The experimental equilibrium constants for ion-pair formation were corrected according to the Fuoss equation. The calculated equilibrium constants for the formation of free ions were taken as a quantitative measure of the base strength in IL solutions and compared with the relative constants in water. The effect of IL composition is discussed for a series of fixed IL anions and fixed IL cations. Finally, the sensitivity of the proton transfer reaction to the electronic effects of the substituent groups on the pyridine ring was quantified by applying the Hammett equation. A more marked levelling effect on the base strength was observed in ILs than in water. The Hammett reaction constants 1 were then correlated with solvent parameters according to a multi-parametric analysis, which showed that both specific hydrogen-bond donor/acceptor and nonspecific interactions play an important role, with a and permittivity being the main parameters affecting the ability of the IL to differentiate the strength of the base

Liposome Destabilization by a 2,7-Diazapyrenium Derivative Through Formation of Transient Pores in the Lipid Bilayer

The effect of the luminescent heteroaromatic electron acceptor N,N 0 -dimethyl-2,7-diazapyrenium dichloride ) on the stability of 1-palmitoyl-2-oleoylphosphatydilcholine (POPC) liposomes is determined on the basis of the rate of release of different fluorescent probes entrapped within the liposome. The experiments show that DM-DAP 2þ exerts a substantial destabilizing action on the liposomal bilayer, particularly at low concentrations. Molecular dynamics simulations suggest that the activity of DM-DAP 2þ is related to its tendency to surround itself with water molecules, conceivably favoring the formation of transient pores across the bilayer

Effect of the Incorporation of Functionalized Cyclodextrins in the Liposomal Bilayer

Liposomes loaded with drug–cyclodextrin complexes are widely used as drug delivery systems, especially for species with low aqueous solubility and stability. Investigation of the intimate interactions of macrocycles with liposomes are essential for formulation of efficient and stable drug-in-cyclodextrin-in-liposome carriers. In this work, we reported the preparation of unilamellar vesicles of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) embedded with native β-cyclodextrin and two synthetic derivatives: heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TMCD) and heptakis(2,3-di-O-acetyl)-β-cyclodextrin (DACD). We then studied the effect of these macrocycles on the liposomal size, membrane viscosity, and liposomal stability at different temperatures and concentrations. We observed that TMCD and DACD affected vesicle size and the change of size was related to CD concentration. Irrespective of its nature, the macrocycle established interactions with the phospholipidic head groups, preventing cyclodextrins to diffuse into the lipid bilayer, as confirmed by molecular dynamics simulations. Such supramolecular structuring improves liposome stability making these colloid systems promising carriers for biologically active compounds

Micellization properties of cardanol as a renewable co-surfactant

With the aim to improve the features of surfactant solutions in terms of sustainability and renewability we propose the use of the hydrogenated natural and sustainable plant-derived cardanol as an additive to commercial surfactants. In the present study we demonstrated that its addition, in amount as high as 10%, to commercial surfactants of different charge do not significantly affect surfactant properties. Conversely, the presence of hydrogenated cardanol can strongly affect spectrophotometric determination of CMC if preferential interactions with the elected dyes take place. This latter evidence may be profitably exploited in the surfactant manufacturing by considering that the concurrent presence of a rigid organic molecule such as Orange OT and 10% hydrogenated cardanol decreases the CMC of CTAB up to 65 times

Liposomes loaded with the proteasome inhibitor z-leucinyl-leucinyl-norleucinal are effective in inducing apoptosis in colorectal cancer cell lines

Colorectal cancer (CRC) is one of the main causes of cancer-related death in developed countries. Targeted therapies and conventional chemotherapeutics have been developed to help treat this type of aggressive cancer. Among these, the monoclonal antibodies cetuximab (Cxm) and panitumumab specifically target and inactivate the signaling of ERBB1 (EGF receptor), a key player in the development and progression of this cancer. Unfortunately, these antibodies are effective only on a small fraction of patients due to primary or secondary/acquired resistance. However, as ERBB1 cell surface expression is often maintained in resistant tumors, ERBB1 can be exploited as a target to deliver other drugs. Liposomes and immunoliposomes are under intensive investigation as pharmaceutical nanocarriers and can be functionalized with specific antibodies. In this study, we first investigated the anti-cancer activity of a cell permeable tripeptide, leucine-leucin-norleucinal (LLNle), an inhibitor of gamma-secretase and proteasome, in three different CRC cell lines that express ERBB1. We formulated LLNle-liposomes and Cxm-conjugated LLNle-loaded liposomes (LLNle-immunoliposomes) and evaluated their efficacy in inhibiting cell survival. Despite similar pro-apoptotic effects of free LLNle and LLNle-liposomes, immunoliposomes-LLNle were significantly less effective than their unconjugated counterparts. Indeed, immunoliposomes-LLNle were readily internalized and trafficked to lysosomes, where LLNle was likely trapped and/or inactivated. In conclusion, we demonstrated that LLNle was readily delivered to CRC cell lines by liposomes, but immunoliposomes-LLNle failed to show significant anti-cancer activity. \ua9 2020 by the authors. Licensee MDPI, Basel, Switzerland