The Protein Corona Conundrum: Exploring the Advantages and Drawbacks of its Presence around Amphiphilic Nanoparticles.

The success of targeted drug delivery systems still requires a detailed understanding about the biological consequences of self-developed biomolecular coronas around them, since this is the surface that interacts with living cells. Herein, we report the behavior of carbohydrate-decorated amphiphilic nanoparticles in a plasma environment with regard to the formation and biological consequences of the protein corona. Naked amphiphilic nanoparticles were produced through the self-assembly of azido-PEO900-docosanoate molecules, and the coupling of N-acetylglucosamine via click chemistry enabled the fabrication of the corresponding bioactive glyco-nanostructures. Light scattering measurements, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, liquid chromatography-mass spectrometry, and the Pierce BCA protein assay all confirmed the presence of protein coronas around the self-assembled nanoparticles, regardless of the presence of the sugar residues, although it reduces the amount of adsorbed proteins. The protein coronas were formed mainly by human serum albumin, complement proteins, apolipoproteins, immunoglobulins, and proteins involved in the coagulation cascade (fibrinogen and prothrombin). While the presence of these protein coronas significantly reduced cellular uptake of the amphiphilic assemblies, they also notably reduced the cytotoxic and hemolytic effects that result from the contact of the nanoparticles with living cells. Accordingly, we highlight that protein coronas should not always be treated as artifacts that have to be avoided because they can also provide beneficial effects.

Proton transfer in fluorescent secondary amines: synthesis, photophysics, theoretical calculation and preparation of photoactive phosphatidylcholine-based liposomes.

In this article, new fluorescent lipophilic based benzazoles were synthesized from the reaction between photoactive formyl derivatives and aliphatic amines followed by NaBH4 reduction with good yields. The photophysics of the benzazoles was investigated experimentally and theoretically. These compounds present absorption maxima in the UV region (∼339 nm) and fluorescence emission maxima in the cyan to green region with a large Stokes shift (∼175 nm) due to a proton transfer process in the excited state. Two fluorophores were successfully used as a proof of concept to produce stable photoactive liposomes prepared from phosphatidylcholine (PC) and were characterized by zeta potential, small angle X-ray scattering (SAXS), FTIR and UV-Vis experiments (turbidity). The scattering data indicate that the presence of compounds 20 and 23 reduces the overall surface charge of the PC vesicles, possibly due to the partial neutralization of phosphatidic acid and/or phosphatidylinositol phosphate by the amine groups, and they also modify the structural features of the assemblies, leading, in particular, to a reduction in the thickness of the hydrophobic inner segment (tt) of the liposomes. DFT and TD-DFT calculations were performed with the ωB97XD functional. Geometric analyses show that the 2-(2'-hydroxyphenyl)benzazolic planar portion allows an effective ππ* electronic transition. Additionally, the calculations indicate a small energy barrier to proton transfer. The results of the absorption and emission maxima show a slight solvent influence on the wavelengths.

Gold nanoparticles and/or N-acetylcysteine mediate carrageenan-induced inflammation and oxidative stress in a concentration-dependent manner.

We report the effect of gold nanoparticles (AuNP) in an acute inflammation model induced by carrageenan (CG) and compared this effect with those induced by the antioxidant N-acetylcysteine (NAC) alone and by the synergistic effect of NAC and AuNP together. Male Wistar rats received saline or saline containing CG administered into the pleural cavity, and some rats also received NAC (20 mg/kg) subcutaneously and/or AuNP administered into the pleural cavity immediately after surgery. Four hours later, the rats were sacrificed and pleural exudates obtained for evaluation of cytokine levels and myeloperoxidase activities. Oxidative stress parameters were also evaluated in the lungs. The results demonstrated that the inflammatory process caused by the administration of CG into the pleural cavity resulted in a substantial increase in the levels of tumor necrosis factor-α, interleukin-1ß, and myeloperoxidase and a reduction in interleukin-10 levels. These levels seem to be reversed after different treatments in animals. Antioxidant enzymes exhibited positive responses after treatment of NAC + AuNP, and all treatments were effective at reducing lipid peroxidation and oxidation of thiol groups induced by CG. These findings suggest that small compounds, such as NAC plus AuNP, may be useful in the treatment of conditions associated with local inflammation.

Synthesis, micellization and lectin binding of new glycosurfactants.

Here we report the preparation and physico-chemical characterization of carbohydrate-decorated micelles and their interaction with lectins. A library of biosourced amphiphiles was prepared by copper-catalyzed azide-alkyne cycloaddition (CuAAC) between alkynyl sugars (lactose, N-acetyl-D-glucosamine) and azido-functionalized poly(ethylene glycol) esters (N3-PEG900-decanoate (C10) and -dodecanoate (C12)). In water, these glycoconjugates self-assemble into micelles of homogeneous nanometric size (11 nm) as evidenced by scattering techniques (DLS for light, and SAXS for X-ray). A comparative study with previously synthesized octadecanoate counterparts pointed out that that nature of the fatty acid has no significant influence on the particle size but only affects their compactness. These findings are in favor of a possible bulk preparation from lipid mixtures such as those encountered in renewable vegetable oils. The presence of the carbohydrate epitopes on the surface of the micelles and their bioavailability for lectin targeting were also evidenced by light scattering measurements using wheat germ agglutinin (WGA) and peanut (Arachis hypogaea) (PNA) lectins, supporting possible application as targeted drug nanocarriers.

Self-association of sodium deoxycholate with EHEC cellulose cooperatively induced by sodium dodecanoate.

Some aspects of ethyl (hydroxyethyl) cellulose (EHEC) aqueous behavior in the presence of ionic surfactants are described in the literature; however, most of the studies reported address moderately concentrated solutions. Few studies have been carried out in the dilute regime using mixtures of biosurfactants. The main purpose of this work is to investigate the interaction of EHEC in the dilute regime and to verify the mixture of two surfactants: sodium deoxycholate (NaDC) and sodium dodecanoate (SDoD). The parameters of the surfactant to polymer association processes such as the critical aggregation concentration (cac) and saturation of the polymer by surfactants (psp) were determined from the plots of surface tension and specific conductivity versus surfactant concentration in basic conditions. The cmc of NaDC-SDoD mixtures showed non-ideal behavior. However, EHEC added to mixtures of SDoD and NaDC acts as a stabilizer for the mixed aggregate during the association process.

Self-assembly of amphiphilic glycoconjugates into lectin-adhesive nanoparticles.

This work describes the synthesis and self-assembly of carbohydrate-clicked rod-coil amphiphilic systems. Copper-catalyzed Huisgen cycloaddition was efficiently employed to functionalize the hydrophilic extremity of PEG-b-tetra(p-phenylene) conjugates by lactose and N-acetyl-glucosamine ligands. The resulting amphiphilic systems spontaneously self-assembled into nanoparticles when dissolved in aqueous media, as evidenced by dynamic light scattering (DLS), transmission electron microscopy (TEM), and small-angle X-ray scattering (SAXS). The formation of highly monodisperse micelles having a mean diameter of 10 nm was observed for systems containing a PEG 900 core, and a decrease in the hydrophilic moiety (PEG 600) led to the formation of vesicles with a broader size distribution. The presence of carbohydrate residues on the surfaces of the micelles and their ability to establish specific interactions with wheat germ agglutinin (WGA) and peanut agglutinin (PNA) were further highlighted by light-scattering measurements, thus confirming the attractive applications of such sugar micelles in biosensor devices.