Sphingomyelin nanosystems decorated with TSP-1 derived peptide targeting senescent cells.

Senescent cells accumulation can contribute to the development of several age-related diseases, including cancer. Targeting and eliminating senescence cells, would allow the development of new therapeutic approaches for the treatment of different diseases. The 4N1Ks peptide, a 10 amino acid peptide derived from TSP1 protein, combines both features by targeting the CD47 receptor present in the surface of senescent cells and demonstrating senolytic activity, thereby representing a new strategy to take into account. Nonetheless, peptide drugs are known for their biopharmaceutical issues, such as low short half-life and tendency to aggregate, which reduces their bioavailability and limits their therapeutic potential. In order to overcome this problem, herein we propose the use of biodegradable and biocompatible sphingomyelin nanosystems (SNs), decorated with this peptide for the targeting of senescent cells. In order to efficiently associate the 4N1Ks peptide to the nanosystems while exposing it on their surface for an effective targeting of senescent cells, the 4N1Ks peptide was chemically conjugated to a PEGylated hydrophobic chain. The resulting SNs-4N1Ks (SNs-Ks), were extensively characterized for their physicochemical properties, by dynamic light scattering, multiple-angle dynamic light scattering, nanoparticle tracking analysis and atomic force microscopy. The SNs-Ks demonstrated suitable features in terms of size (∼100 nm), association efficiency (87.2 ± 6.9%) and stability in different biorelevant media. Cell toxicity experiments in MCF7 cancer cells indicated an improved cytotoxic effect of SNs-Ks, decreasing cancer cells capacity to form colonies, with respect to free peptide, and an improved hemocompatibility. Lastly, senescence escape preliminary experiments demonstrated the improvement of SNs-Ks senolytic activity of in chemotherapy-induced senescence model of breast cancer cells. Therefore, these results demonstrate for the first time the potential of the combination of SNs with 4N1Ks peptide for the development of innovative senolytic therapies to battle cancer.

Exploiting the Potential of Supported Magnetic Nanomaterials as Fenton-Like Catalysts for Environmental Applications.

In recent years, the application of magnetic nanoparticles as alternative catalysts to conventional Fenton processes has been investigated for the removal of emerging pollutants in wastewater. While this type of catalyst reduces the release of iron hydroxides with the treated effluent, it also presents certain disadvantages, such as slower reaction kinetics associated with the availability of iron and mass transfer limitations. To overcome these drawbacks, the functionalization of the nanocatalyst surface through the addition of coatings such as polyacrylic acid (PAA) and their immobilization on a mesoporous silica matrix (SBA15) can be factors that improve the dispersion and stability of the nanoparticles. Under these premises, the performance of the nanoparticle coating and nanoparticle-mesoporous matrix binomials in the degradation of dyes as examples of recalcitrant compounds were evaluated. Based on the outcomes of dye degradation by the different functionalized nanocatalysts and nanocomposites, the nanoparticles embedded in a mesoporous matrix were applied for the removal of estrogens (E1, E2, EE2), accomplishing high removal percentages (above 90%) after the optimization of the operational variables. With the feasibility of their recovery in mind, the nanostructured materials represented a significant advantage as their magnetic character allows their separation for reuse in different successive sequential batch cycles.

Reusable Fe3O4/SBA15 Nanocomposite as an Efficient Photo-Fenton Catalyst for the Removal of Sulfamethoxazole and Orange II.

Today, the presence of recalcitrant pollutants in wastewater, such as pharmaceuticals or other organic compounds, is one of the main obstacles to the widespread implementation of water reuse. In this context, the development of innovative processes for their removal becomes necessary to guarantee effluent quality. This work presents the potentiality of magnetic nanoparticles immobilized on SBA-15 mesoporous silica as Fenton and photo-Fenton catalysts under visible light irradiation. The influence of the characteristics of the compounds and nanoparticles on the removal yield was investigated. Once the key aspects of the reaction mechanism were analyzed, to evaluate the feasibility of this process, an azo dye (Orange II) and an antibiotic (sulfamethoxazole) were selected as main target compounds. The concentration of Orange II decreased below the detection limit after two hours of reaction, with mineralization values of 60%. In addition, repeated sequential experiments revealed the recoverability and stability of the nanoparticles in a small-scale reactor. The benchmarking of the obtained results showed a significant improvement of the process using visible light in terms of kinetic performance, comparing the results to the Fenton process conducted at dark. Reusability, yield and easy separation of the catalyst are its main advantages for the industrial application of this process.

A nanoemulsion/micelles mixed nanosystem for the oral administration of hydrophobically modified insulin.

The potential of nanoemulsions for the oral administration of peptides is still in its early stage. The aim of the present work was to rationally design, develop, and fully characterize a new nanoemulsion (NE) intended for the oral administration of hydrophobically modified insulin (HM-insulin). Specific components of the NE were selected based on their enhancing permeation properties as well as their ability to improve insulin association efficiency (Miglyol 812, sodium taurocholate), stability in the intestinal fluids, and mucodiffusion (PEGylated phospholipids and poloxamer 407). The results showed that the NE co-existed with a population of micelles, forming a mixed system that exhibited a 100% of HM-insulin association efficiency. The nanosystem showed good stability and miscibility in different bio-relevant media and displayed an acceptable mucodiffusive behavior in porcine mucus. In addition, it exhibited a high interaction with cell mono-cultures (Caco -2 and C2BBe1 human colon carcinoma Caco-2 clone cells) and co-cultures (C2BBe1 human colon carcinoma Caco-2 clone/HT29-MTX cells). The internalization in Caco-2 monolayers was also confirmed by confocal microscopy. Finally, the promising in vitro behavior of the nanosystem in terms of overcoming the biological barriers of the intestinal tract was translated into a moderate, although significant, hypoglycemic response (≈ 20-30%), following intestinal administration to both healthy and diabetic rat models. Overall, this information underlines the crucial steps to address when designing peptide-based nanoformulations to successfully overcome the intestinal barriers associated to the oral modality of administration.

Novel Supramolecular Nanoparticles Derived from Cucurbit[7]uril and Zwitterionic Surfactants.

Binding constants, log K ≈ 6.6 M-1, and NMR characterization of the complexes formed by sulfobetaines and cucurbit[7]uril (CB7) support the electrostatic interaction as the major driving force. This very strong binding motif is cross-linked by additional CB7 molecules, resulting in the formation of supramolecular nanoparticles (SNPs) with an average diameter of 172 nm and a negative surface potential. The time course evolution of the particle size and the surface potential suggests the very fast formation of an amorphous aggregate that absorbs an additional amount of sulfobetaine. These aggregates afford very stable (more than 2 weeks) nanoparticles in an aqueous dispersion. The reversibility of the sulfobetaine/CB7 host/guest complexes allows SNP disaggregation by adding a competitive guest as shown by treatment with tetraethylammonium chloride. The addition of this competitive cation triggers a SNP-to-micelle transition. The potential application of these nanoparticles as drug delivery vehicles was investigated by using carboxyfluorescein. These experiments revealed that upon externally induced disruption of the SNPs (by tetraethylammonium chloride) the fluorescent dye was trapped in micellar aggregates that can be further disrupted by cyclodextrin addition.

Gold nanorod synthesis catalysed by Au clusters.

Gold nanorods have been successfully synthesized by the seed mediated method using Au clusters. This synthesis does not require silver ions to obtain large amounts of Au nanorods and has good control over their aspect ratio. Au clusters are produced with the same recipe as for Au seeds, but using shorter reaction times. This very simple scheme confirms the important catalytic influence of clusters in the anisotropic growth control.

Self-Assembly of Silver Metal Clusters of Small Atomicity on Cyclic Peptide Nanotubes.

Subnanometric noble metal clusters, composed by only a few atoms, behave like molecular entities and display magnetic, luminescent and catalytic activities. However, noncovalent interactions of molecular metal clusters, lacking of any ligand or surfactant, have not been seen at work. Theoretically attractive and experimentally discernible, van der Waals forces and noncovalent interactions at the metal/organic interfaces will be crucial to understand and develop the next generation of hybrid nanomaterials. Here, we present experimental and theoretical evidence of noncovalent interactions between subnanometric metal (0) silver clusters and aromatic rings and their application in the preparation of 1D self-assembled hybrid architectures with ditopic peptide nanotubes. Atomic force microscopy, fluorescence experiments, circular dichroism and computational simulations verified the occurrence of these interactions in the clean and mild formation of a novel peptide nanotube and metal cluster hybrid material. The findings reported here confirmed the sensitivity of silver metal clusters of small atomicity toward noncovalent interactions, a concept that could find multiple applications in nanotechnology. We conclude that induced supramolecular forces are optimal candidates for the precise spatial positioning and properties modulation of molecular metal clusters. The reported results herein outline and generalize the possibilities that noncovalent interactions will have in this emerging field.

Characterization and cytotoxicity studies on liposome-hydrophobic magnetite hybrid colloids.

The aim of this study was to highlight the main features of magnetoliposomes prepared by TLE, using hydrophobic magnetite, and stabilized with oleic acid, instead of using the usual hydrophilic magnetite surrounded by sodium citrate. These biocompatible magnetoliposomes (MLs) were prepared with the purpose of producing a magnetic carrier capable of loading either hydrophilic or lipophilic drugs. The effect of different liposome/magnetite weight ratios on the stability of magnetoliposomes was evaluated by monitoring the mean diameter of the particles, their polydispersity index, and zeta potential over time. The prepared magnetoliposomes showed a high liposome-magnetite association, with magnetoliposomes containing PEG (polyethylene glycol) showing the best magnetite loading values. To verify the position of magnetite nanoparticles in the vesicular structures, the morphological characteristics of the structures were studied using transmission electron microscopy (TEM). TEM studies showed a strong affinity between hydrophobic magnetite nanoparticles, the surrounding oleic acid molecules, and phospholipids. Furthermore, the concentration above which one would expect to find a cytotoxic effect on cells as well as morphological cell-nanoparticle interactions was studied in situ by using the trypan blue dye exclusion assay, and the Prussian Blue modified staining method.

Coupling of carbon and peptide nanotubes.

Two of the main types of nanotubular architectures are the single-walled carbon nanotubes (SWCNTs) and the self-assembling cyclic peptide nanotubes (SCPNs). We here report the preparation of the dual composite resulting from the ordered combination of both tubular motifs. In the resulting architecture, the SWCNTs can act as templates for the assembly of SCPNs that engage the carbon nanotubes noncovalently via pyrene "paddles", each member of the resulting hybrid stabilizing the other in aqueous solution. The particular hybrids obtained in the present study formed highly ordered oriented arrays and display complementary properties such as electrical conductivity. Furthermore, a self-sorting of the cyclic peptides toward semiconducting rather than metallic SWCNTs is also observed in the aqueous dispersions. It is envisaged that a broad range of exploitable properties may be achieved and/or controlled by varying the cyclic peptide components of similar SWCNT/SCPN hybrids.

Novel catanionic vesicles from calixarene and single-chain surfactant.

The mixed system between p-sulfonatocalix[4]arene and tetradecyltrimethylammonium bromide forms unilamellar vesicles after sonication of the aqueous dispersion. Furthermore these vesicles can be stored, without use of lyoprotectants, by lyophilization and then rehydration without change in size or shape.

Synthesis of small atomic copper clusters in microemulsions.

We report evidence of the formation of small atomic copper clusters, Cu(n), by the microemulsion technique, and how their size can be controlled by adjusting the percentage of the reducing agent used. Copper clusters were characterized by UV-visible spectrophotometry and atomic force microscopy. Photoluminescent copper clusters, Cu(n), with n less, similar 13, can be obtained using very low percentages of the reducing agent (<10% of the stochiometric amount). Photoluminescent clusters disappear for larger percentages of reducing agent, giving rise to larger copper clusters (0.8-2.0 nm), showing a red-shift of their UV-visible absorption bands as they grow in size. Finally, by using near stoichiometric amounts, nanoparticles of 2.9 +/- 1.1 nm in size, displaying the characteristic plasmon band, can be obtained.

Synthesis of atomic gold clusters with strong electrocatalytic activities.

Small atomic gold clusters in solution, Au n , stabilized by tetrabutyl ammonium bromide (TBABr), have been synthesized by a simple electrochemical technique, based on the anodic dissolution of a gold electrode in the presence of TBABr salt, and using acetronitrile as solvent. The presence of clusters in the range Au3-Au11 were detected by MALDI-TOF spectroscopy, and further characterized by UV-vis absorption spectroscopy, TEM, AFM, X-ray diffraction, and cyclic voltammetry. Clusters display a semiconductor behavior with a band edge of approximately 2.5 eV. We report here their extraordinarily high electrocatalytic activity toward the O2 reduction reaction in acid solutions, which can explain Zhang's results, showing that a four-electron mechanism seems to occur because of the facile reduction of H2O2 on gold clusters compared to bulk gold or larger gold nanoparticles.