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Metallic nano multilayers were usually prepared by dual targets alternating deposition method. In this paper, a series of self-assembled Cu–W nano multilayers with different modulation periods were deposited on single crystal silicon substrate by dual targets confocal magnetron sputtering technique. The self-assembled film presented an alternation of W-rich layer and Cu-rich layer. The degree of coherence of the layered interface can be adjusted by controlling both the solid solubility of W-rich and Cu-rich layers. The film resistance increment of the self-assembled Cu–W multilayers is only 14% when the modulation period decreases from 68.2 nm to 5.3 nm, having less size effect compared to the film prepared by alternating deposition method. It noticed that the film resistance even decreased slightly when the modulation period decreased to below 5.3 nm. These results suggested that the coherence could weak the interface scattering ability to electrons, so the self-assembled Cu–W multilayers have lower resistance than the multilayer prepared by alternating deposition technique. This study presented a new pathway to enhance the conductivity of the multilayers.

Altres ajuts: acords transformatius de la UAB Altres ajuts: EU COST Action CA 17140 ; ICREA Academia award Nanobodies represent valuable tools in advanced therapeutic strategies but their small size (∼2.5 × ∼ 4 nm) and limited valence for interactions might pose restrictions for in vivo applications, especially regarding their modest capacity for multivalent and cooperative interaction. In this work, modular protein constructs have been designed, in which nanobodies are fused to protein domains to provide further functionalities and to favor oligomerization into stable self-assembled nanoparticles. The nanobody specificity for their targets is maintained in such supramolecular complexes. Also, their diameter around 70 nm and multivalent interactivity should favor binding and penetrability into target cells via solvent-exposed receptor. These concepts have been supported by unrelated nanobodies directed against the ricin toxin (A3C8) and the Her2 receptor (EM1), respectively, that were modified with the addition of a reporter protein and a hexa-histidine tag at the C-terminus that promotes self-assembling. The A3C8-based nanoparticles neutralize the ricin toxin efficiently, whereas the EM1-based nanoparticles enable to selective imaging Her2-positive cells. These findings support the excellent extracellular and intracellular functionality of nanobodies organized in form of oligomeric nanoscale assemblies.

Peptide-based hydrogels (PHGs) are biocompatible materials suitable for biological, biomedical, and biotechnological applications, such as drug delivery and diagnostic tools for imaging. Recently, a novel class of synthetic hydrogel-forming amphiphilic cationic peptides (referred to as series K), containing an aliphatic region and a Lys residue, was proposed as a scaffold for bioprinting applications. Here, we report the synthesis of six analogues of the series K, in which the acetyl group at the N-terminus is replaced by aromatic portions, such as the Fmoc protecting group or the Fmoc-FF hydrogelator. The tendency of all peptides to self-assemble and to gel in aqueous solution was investigated using a set of biophysical techniques. The structural characterization pointed out that only the Fmoc-derivatives of series K keep their capability to gel. Among them, Fmoc-K3 hydrogel, which is the more rigid one (G’ = 2526 Pa), acts as potential material for tissue engineering, fully supporting cell adhesion, survival, and duplication. These results describe a gelification process, allowed only by the correct balancing among aggregation forces within the peptide sequences (e.g., van der Waals, hydrogen bonding, and π–π stacking).

Background In recent years, multifunctional theranostic nanoparticles have been fabricated by integrating imaging and therapeutic moieties into one single nano-formulations. However, Complexity of production and safety issues limits their further application. Results Herein, we demonstrated self-assembled nanoparticles with single structure as a “from one to all” theranostic platform for tumor-targeted dual-modal imaging and programmed photoactive therapy (PPAT). The nanoparticles were successfully developed through self-assembling of hyaluronic acid (HA)-cystamine-cholesterol (HSC) conjugate, in which IR780 was simultaneously incorporated (HSCI NPs). Due to the proper hydrodynamic size and intrinsic targeting ability of HA, the HSCI NPs could accumulate at the tumor site effectively after systemic administration. In the presence of incorporated IR780, in vivo biodistribution and accumulation behaviors of HSCI NPs could be monitored by photoacoustic imaging. After cellular uptake, the HSCI NPs would disintegrate resulting from cystamine reacting with over-expressed GSH. The released IR780 would induce fluorescence “turn-on” conversion, which could be used to image tumor sites effectively. Upon treatment with 808 nm laser irradiation, PPAT could be achieved in which generated reactive oxygen species (ROS) would produce photodynamic therapy (PDT), and subsequently the raised temperature would be beneficial to tumor photothermal therapy (PTT). Conclusion The self-assembled HSCI NPs could act as “from one to all” theranostic platform for high treatment efficiency via PPAT pattern, which could also real-time monitor NPs accumulation by targeted and dual-modal imaging in a non-invasive way. Electronic supplementary material The online version of this article (10.1186/s12951-019-0450-x) contains supplementary material, which is available to authorized users.

Long (15 - 40 μm), thin (diameter of 20 ± 5 nm), and well-dispersed CuNWs Cu nanowires were prepared. The high-resolution TEM and selected area electron diffraction showed that the CuNWs were single-crystalline. To investigate the growth mechanism, we examined the microstructure of these CuNWs at different reaction time. It was found that the CuNWs were actually formed through the self-assembling of Cu nanoparticles along the [110] direction. The transparent electrodes fabricated using the CuNWs achieved a high transparency of 76 % at 31±5 Ω/□.

Chronic wounds represent a major health burden and drain on medical system. Efficient wound repair is only possible if the dressing materials target simultaneously multiple factors involved in wound chronicity, such as deleterious proteolytic and oxidative enzymes and high bacterial load. Here we develop multifunctional hydrogels for chronic wound management through self-assembling of thiolated hyaluronic acid (HA-SH) and bioactive silver-lignin nanoparticles (Ag@Lig NPs). Dynamic and reversible interactions between the polymer and Ag@Lig NPs yield hybrid nanocomposite hydrogels with shear-thinning and self-healing properties, coupled to zero-order kinetics release of antimicrobial silver in response to infection-related hyalurodinase. The hydrogels inhibit the major enzymes myeloperoxidase and matrix metalloproteinases responsible for wound chronicity in a patient's wound exudate. Furthermore, the lignin-capped AgNPs provide the hydrogel with antioxidant properties and strong antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. The nanocomposite hydrogels are not toxic to human keratinocytes after 7 days of direct contact. Complete tissue remodeling and restoration of skin integrity is demonstrated in vivo in a diabetic mouse model. Hematological analysis reveals lack of wound inflammation due to bacterial infection or toxicity, confirming the potential of HA-SH/Ag@Lig NPs hydrogels for chronic wound management. Statement of significance Multifunctional hydrogels are promising materials to promote healing of complex wounds. Herein, we report simple and versatile route to prepare biocompatible and multifunctional self-assembled hydrogels for efficient chronic wound treatment utilizing polymer-nanoparticle interactions. Hybrid silver-lignin nanoparticles (Ag@Lig NPs) played both: i) structural role, acting as crosslinking nodes in the hydrogel and endowing it with shear-thinning (ability to flow under applied shear stress) and self-healing properties, and ii) functional role, imparting strong antibacterial and antioxidant activity. Remarkably, the in situ self-assembling of thiolated hyaluronic acid and Ag@Lig NPs yields nanocomposite hydrogels able to simultaneously inhibits the major factors involved in wound chronicity, namely the overexpressed deleterious proteolytic and oxidative enzymes, and high bacterial load.

Green fluorescent protein (GFP) is a widely used scaffold for protein-based targeted nanomedicines because of its high biocompatibility, biological neutrality and outstanding structural stability. However, being immunogenicity a major concern in the development of drug carriers, the use of exogenous proteins such as GFP in clinics might be inadequate. Here we report a human nidogen-derived protein (HSNBT), rationally designed to mimic the structural and functional properties of GFP as a scaffold for nanomedicine. For that, a GFP-like β-barrel, containing the G2 domain of the human nidogen, has been rationally engineered to obtain a biologically neutral protein that self-assembles as 10nm-nanoparticles. This scaffold is the basis of a humanized nanoconjugate, where GFP, from the well-characterized protein T22-GFP-H6, has been substituted by the nidogen-derived GFP-like HSNBT protein. The resulting construct T22-HSNBT-H6, is a humanized CXCR4-targeted nanoparticle that selectively delivers conjugated genotoxic Floxuridine into cancer CXCR4+ cells. Indeed, the administration of T22-HSNBT-H6-FdU in a CXCR4-overexpressing colorectal cancer mouse model results in an even more efficient selective antitumoral effect than that shown by its GFP-counterpart, in absence of systemic toxicity. Therefore, the newly developed GFP-like protein scaffold appears as an ideal candidate for the development of humanized protein nanomaterials and successfully supports the tumor-targeted nanoscale drug T22-HSNBT-H6-FdU., Patricia Álamo and Juan Cedano contributed equally to this work. The authors are indebted to Agencia Estatal de Investigación (AEI) and to Fondo Europeo de Desarrollo Regional (FEDER) (grant BIO2016-76063-R, AEI/FEDER, UE), to AGAUR (2017SGR-229) and CIBER-BBN (project NANOPROTHER), granted to AV, to CIBER-BBN (project NANOSCAPE and NANOLINK) and ISCIII (PI20/00400 co-funding FEDER) granted to UU, to ISCIII (PI15/00272 co-founding FEDER) granted to EV and to ISCIII (PIE15/00028 and PI18/00650, co-funding FEDER) and AGAUR (2017 SGR 865 GRC) granted to RM. We are also indebted to CERCA programme (Generalitat de Catalunya) and to the Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) that is an initiative funded by the VI National R&D&I Plan 2008–2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Carlos III, with assistance from the European Regional Development Fund. We also appreciate the support from the COST-Action Nano2Clinics. Protein production has been partially performed by the ICTS “NANBIOSIS”, more specifically by the Protein Production Platform of CIBER in Bioengineering, Biomaterials & Nanomedicine (CIBER-BBN)/ IBB, at the UAB sePBioEs scientific-technical service (http://www.nanbiosis.es/portfolio/u1-protein-production-platform-ppp/), and the nanoparticle size analysis by the Biomaterial Processing and Nanostructuring Unit. Synthesis of thiolated oligo-FdU was performed by the ICTS NANBIOSIS Oligonucleotide Synthesis Platform (CIBER-BBN). The in vivo work was performed by the ICTS NANBIOSIS of the CIBER-BBN Nanotoxicology Unit (http://www.nanbiosis.es/portfolio/u18-nanotoxicology-unit/). We are indebted to Servei de Microscopia from UAB for their excellent confocal and electronic microscopy services. We are also indebted to Servei de Cultius Celulars i Anticossos (SCAC) form UAB for their excellent cell culture and flow cytometry facilities and especially to Fran Cortes for his excellent technical support. We are thankful to Dra. Marta Taulés from CCiT-UB for her help in SPR experiments and analysis. We are also thankful to Luis Carlos Navas from Institut d'Investigacions biomèdiques Sant Pau (IIB Sant Pau) for his technical support in immunohistochemistry experiments. UU and LMCD were supported by Miguel Servet (CP19/00028) and PFIS (FI19/00148) contracts respectively from ISCIII co-funded by European Social Fund (ESF investing in your future). NS was supported by a pre-doctoral fellowship from the Government of Navarra and LAC was supported by AECC Scientific Foundation grant postdoctoral fellow. AV received an ICREA ACADEMIA award.

The review will first discuss shortly the phenomenon of corrosion and enroll some general possibilities to decrease the rate of this deterioration. The stress will be laid upon the presentation of anticorrosive self-assembled molecular (SAM) layers as well as on the preparation technology that is a simple technique, does not need any special device, and can be applied on different solids (metals or non-metals) alone or in combination. The paper groups the chemicals (mainly amphiphiles) that can develop nanolayers on different pure or oxidized metal surfaces. The history of the self-assembled molecular layer will be discussed from the beginning of the first application up to now. Not only the conditions of the nanofilm preparation as well as their characterization will be discussed, but the methods that can evaluate the corrosion-inhibiting efficiency of the SAM layers under a corrosive environment will be demonstrated as well.

Producción Científica, Self-assembling bioinks offer the possibility to biofabricate with molecular precision, hierarchical control, and biofunctionality. For this to become a reality with widespread impact, it is essential to engineer these ink systems ensuring reproducibility and providing suitable standardization. We have reported a self-assembling bioink based on disorder-to-order transitions of an elastin-like recombinamer (ELR) to co-assemble with graphene oxide (GO). Here, we establish reproducible processes, optimize printing parameters for its use as a bioink, describe new advantages that the self-assembling bioink can provide, and demonstrate how to fabricate novel structures with physiological relevance. We fabricate capillary-like structures with resolutions down to ∼10 µm in diameter and ∼2 µm thick tube walls and use both experimental and finite element analysis to characterize the printing conditions, underlying interfacial diffusion-reaction mechanism of assembly, printing fidelity, and material porosity and permeability. We demonstrate the capacity to modulate the pore size and tune the permeability of the resulting structures with and without human umbilical vascular endothelial cells. Finally, the potential of the ELR-GO bioink to enable supramolecular fabrication of biomimetic structures was demonstrated by printing tubes exhibiting walls with progressively different structure and permeability., The work was supported by the ERC Starting Grant (STROFUNSCAFF), the Medical Research Council (UK Regenerative Medicine Platform Acellular/Smart Materials 3D Architecture, MR/R015651/1), and the AO Foundation AOCMF-17-19M.

Self-assembling processes are ubiquitous phenomena that drive the organization and the hierarchical formation of complex molecular systems. The investigation of assembling dynamics, emerging from the interactions among biomolecules like amino-acids and polypeptides, is fundamental to determine how a mixture of simple objects can yield a complex structure at the nano-scale level. In this paper we present HyperBeta, a novel open-source software that exploits an innovative algorithm based on hyper-graphs to efficiently identify and graphically represent the dynamics of $$\beta$$ β -sheets formation. Differently from the existing tools, HyperBeta directly manipulates data generated by means of coarse-grained molecular dynamics simulation tools (GROMACS), performed using the MARTINI force field. Coarse-grained molecular structures are visualized using HyperBeta ’s proprietary real-time high-quality 3D engine, which provides a plethora of analysis tools and statistical information, controlled by means of an intuitive event-based graphical user interface. The high-quality renderer relies on a variety of visual cues to improve the readability and interpretability of distance and depth relationships between peptides. We show that HyperBeta is able to track the $$\beta$$ β -sheets formation in coarse-grained molecular dynamics simulations, and provides a completely new and efficient mean for the investigation of the kinetics of these nano-structures. HyperBeta will therefore facilitate biotechnological and medical research where these structural elements play a crucial role, such as the development of novel high-performance biomaterials in tissue engineering, or a better comprehension of the molecular mechanisms at the basis of complex pathologies like Alzheimer’s disease.

Self-assembling peptides can be used to design new materials for medical and biological applications. Here we synthesized and characterized two novel cyclic γ-peptides (γ-CPs) with hydrophobic inner surfaces. The NMR and FT-IR studies confirmed that the CPs could self-assemble into parallel stacking structures via intermolecular H-bonds and π-π interactions. The morphologies of the self-assembly CPs showed bundles of nanotubes via transmission electron microscopy (TEM); these nanotubes form water channels to transport water across the lipid membrane. The properties of blocking the transport of protons like natural water channels showed that the hydrophobic inner surfaces are important in artificial transmembrane water channel designs. These studies also showed that water transport was a function of pore size and length of the assemblies.

Fluorescent proteins are useful imaging and theranostic agents, but their potential superiority over alternative dyes is weakened by substantial photobleaching under irradiation. Enhancing protein photostability has been attempted through diverse strategies, with irregular results and limited applicability. In this context, we wondered if the controlled oligomerization of Green Fluorescent Protein (GFP) as nanoscale supramolecular complexes could stabilize the fluorophore through the newly formed protein-protein contacts, and thus, enhance its global photostability. For that, we have here analyzed the photobleaching profile of several GFP versions, engineered to self-assemble as tumour-homing nanoparticles with different targeting, size and structural stability. This has been done under prolonged irradiation in confocal laser scanning microscopy and by small-angle X-ray scattering. The results show that the oligomerization of GFP at the nanoscale enhances, by more than seven-fold, the stability of fluorescence emission. Interestingly, GFP nanoparticles are much more resistant to X-ray damage than the building block counterparts, indicating that the gained photostability is linked to enhanced structural resistance to radiation. Therefore, the controlled oligomerization of self-assembling fluorescent proteins as protein nanoparticles is a simple, versatile and powerful method to enhance their photostability for uses in precision imaging and therapy. Statement of significance Fluorescent protein assembly into regular and highly symmetric nanoscale structures has been identified to confer enhanced structural stability against radiation stresses dramatically reducing their photobleaching. Being this the main bottleneck in the use of fluorescent proteins for imaging and theranostics, this protein architecture engineering principle appears as a powerful method to enhance their photostability for a broad applicability in precision imaging, drug delivery and theranostics. (C) 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Altres ajuts: EU COST Action CA 17140. Villaverde A received an ICREA ACADEMIA award. Unzueta was supported by PERIS program from the Health Department of la Generalitat de Catalunya. Modular protein engineering is suited to recruit complex and multiple functionalities in single-chain polypeptides. Although still unexplored in a systematic way, it is anticipated that the positioning of functional domains would impact and refine these activities, including the ability to organize as supramolecular entities and to generate multifunctional protein materials. To explore this concept, we have repositioned functional segments in the modular protein T22-GFP-H6 and characterized the resulting alternative fusions. In T22-GFP-H6, the combination of T22 and H6 promotes self-assembling as regular nanoparticles and selective binding and internalization of this material in CXCR4-overexpressing tumor cells, making them appealing as vehicles for selective drug delivery. The results show that the pleiotropic activities are dramatically affected in module-swapped constructs, proving the need of a carboxy terminal positioning of H6 for protein self-assembling, and the accommodation of T22 at the amino terminus as a requisite for CXCR4 cell binding and internalization. Furthermore, the failure of self-assembling as regular oligomers reduces cellular penetrability of the fusions while keeping the specificity of the T22-CXCR4 interaction. All these data instruct how multifunctional nanoscale protein carriers can be designed for smart, protein-driven drug delivery, not only for the treatment of CXCR4 human neoplasias, but also for the development of anti-HIV drugs and other pathologies in which CXCR4 is a relevant homing marker.

A new OFF-ON fluorescent chemosensor for ions Hg2+ in water has been designed by associating fluorophore 10-methylacridinium perchlorate (MA+ClO4−) with a selective lipophilic sulfur-containing ligand, such as N,N-bis (2-hydroxyethylthio-1-ethyl)dodecyl amine (DBSO). The communication between the two subunits is only due to their spatial closeness, ensured by sodium dodecyl sulfate (SDS) micellar aggregates. The quenching of MA+ fluorescence is ascribed to a photoinduced electron-transfer from the ligand to the excited fluorophore, still the emission is quickly restored by addition of Hg2+ (as chloride salt) due to the complex formation between ligand and metal. The sensitivity of the system improves by decreasing the ligand concentration, as well as by changing the stoichiometry of the ligand-Hg2+ complex from 1:1 to 2:1. DFT calculations give interesting insights into the structures of the complexes and provide useful information on the sensorial activity experimentally observed. The replacement of MA+ClO4− with 9-cyanoanthracene, a fluorophore differently localized on the micellar aggregate, highlights the effect of Cl− coordination to the complexed Hg2+ on the operating mechanism of the sensor. These results demonstrate as the micellar aggregates provide for a straightforward means to regulate the response of the sensorial system without altering the recognition or reporter unit.

Current therapies fail to eradicate colorectal Cancer Stem Cells (CSCs). One of the proposed reasons for this failure is the selection, by chemotherapy exposure, of resistant cells responsible for tumor recurrence. In this regard, CXCR4 overexpression in tumor associates with resistance and poor prognosis in colorectal cancer (CRC) patients. In this study, the effectiveness of engineered CXCR4-targeted self-assembling toxin nanoparticles has been explored in the selective killing of CXCR4(+) human colon-CSCs compared to 5-Fluorouracil and Oxaliplatin, both classical CRC chemotherapeutic agents. To assess this, 3D spheroid colon-CSCs cultures directly derived from CRC patients and CRC-CSC spheroid-derived tumor mouse models were developed. In these animal models, nanostructured toxins show highly selective induction of pyroptosis in the absence of apoptosis, thus having a great potential to overcome tumor resistance, since the same tumor models show resistance to chemotherapeutics. Results set the basis for further development of more efficient therapies focused on selective CXCR4+ CSCs elimination activating non-apoptotic mechanisms and represent a pre-clinical proof of concept for the use of CSCs-targeted nanostructured toxins as protein drugs for CRC therapy.

There has been a strong interest in methods of creating nanometer scale structures and in particular forming one- and two-dimensional electron confinement structures. Self-organisation has been recognised as a promising way for growing large nanostructure domains with sufficiently regular size and spacing as required for the observation of quantum well states. We investigated the electronic properties and the morphology of Ag nano-structures on c(2 × 2)-N/Cu(001) surface. This system is an example of epitaxial growth confined on nanoscale regions due to the occurrence of an adsorbate induced reconstruction. Using a combination of Scanning Tunneling Microscopy and Angle Resolved Photoemission Spectroscopy techniques we were able to determine the morphology and the growth mode of Ag on N-modified Cu(001) surface and the occurrence of quantum size effects in the electron properties of Ag nanostripes and nanoislands, evidenced in the observation of quantum well states.

This study focuses on the behavior of chitosan (CHI) and its polyelectrolyte complexes with carboxymethyl starch (CMS) used as monolithic matrices with acetaminophen as drug tracer. Two different chitosan grades were tested alone or associated in various ratios with CMS as excipients for tablets obtained by direct compression. The degree of deacetylation (DDA) of CHI, estimated from 1H NMR and FTIR data, was correlated with X-ray diffraction and scanning electron microscopy (SEM) to evaluate structural organization of the monolithic matrices. In vitro drug dissolution assays showed major differences in CHI kinetic profiles between tablets exposed to acidic medium for 2h (to mimick gastric passage) prior to dissolution in simulated intestinal fluid (SIF), and those administered directly to SIF. Prior exposure to acidic SGF conducted to longer dissolution profiles (release completed after 16 h) and preservation of tablet shape, whereas tablets directly incubated in SIF were rapidly disintegrated. The improved properties of chitosan matrices exposed to SGF may be related to an outer compact coating layer (visible in SEM). The effect of self-stabilization of chitosan in acidic medium was compared to that due to formation of polyelectrolyte complexes (PEC) in co-processed polymeric systems (CHI:CMS). The self-formed membrane following exposure to gastric acidity appears to help maintaining tablet integrity and allows higher drug loading, recommending CHI and its complexes with CMS as excipients for drug delivery., Graphical abstract Image 1, Highlights • Chitosan tablets incubated in conditions mimicking gastric residence undergo favorable structural rearrangement. • The effect is stronger in chitosan with higher degree of deacetylation, with better tablet shape and dissolution profiles. • Tablets made with chitosan:carboxymethyl starch are stabilized due to polyelectrolyte complex formation. • Polyelectrolyte complexation is higher at low deacetylation while acidic self-conditioning is stronger at high deacetylation. • Tablets made of chitosan or chitosan:carboxymethyl starch show promise for colonic drug delivery.

The study was aimed at formulating self-assembled capsaicin prodrug nanoparticles (Cap-SSVE NPs) with improved bioavailability, increased antihyperlipidemic activity and less gastrointestinal mucosa irritations. The in vitro release profile of the developed Cap-SSVE NPs was stable in HCl solution (pH 1.2) and distilled water, but very susceptible in PBS (pH 6.8 and 7.4). The relative oral bioavailability of Cap-SSVE NPs was 3.2 folds higher than free capsaicin, with an extended Tmax (0.25–1 h). The Cap-SSVE NPs decreased certain lipid profile indices of both the liver tissue (Total lipids and TG) and the blood sample (TC, TG, LDL and TBA) with elevated levels of HDL in high fat diet induced hyperlipidemic rats. The nanoparticles also predominantly accumulated in the liver with reduced irritations in the gastrointestinal mucosa. Collectively, the formulated Cap-SSVE NPs showed an enhanced bioavailability, increased hypolipidemic effects and reduced mucosa irritations.

Ultrathin films of CdSe nannocrystals (CdSe-NCs) modified with glycosilated molecules have shown interesting electrochemical properties which lead to the detection of lectin Jacalin.

Highly hydrophilic and biocompatible nanocarriers based on polysaccharide hydrogels (nanohydrogels, NHs) were shown to be promising systems for drug delivery applications. Following the idea of these emerging drug carriers, the aim of the present work was to develop self-assembled hydrogel nanoparticles based on amphiphilic derivatives of hyaluronic acid (HA) and riboflavin (Rfv), synthesized by "click" Copper(I)-catalyzed Azide-Alkyne Cycloaddition (CuAAC) reaction. The obtained amphiphilic product (HA-c-Rfv) was able to form nanohydrogels in aqueous environments, in particular by applying an innovative autoclave-based method. HA of different molecular weights (Mw) and degrees of substitution (DS) were prepared and the effect of these parameters on the NHs formation was assessed. The derivative HA220-c-Rfv 40/40 was chosen as the most interesting system, capable to form NHs in the range of 150-200nm and with a negative ζ-potential. NHs were very stable in water solutions and, by adding dextrose as cryoprotectant, it was also possible to freeze-dry the NHs formulation. The developed system is proposed for the delivery of hydrophobic drugs; for this purpose, dexamethasone, piroxicam and paclitaxel were used as model drugs; these molecules were loaded into NHs with high efficiency by film-hydration technique. Furthermore, a HA-c-Rfv derivative bearing an excess of propargylic portions was capable to react with other N3-derivatized molecules, opening the route to a wide spectrum of functionalization opportunities: in this direction, PEG-N3 has been tested as a model molecule for the preparation of PEGylated NHs.

The emergence of bacterial antibiotic resistances is a serious concern in human and animal health. In this context, naturally occurring cationic antimicrobial peptides (AMPs) might play a main role in a next generation of drugs against bacterial infections. Taking an innovative approach to design self-organizing functional proteins, we have generated here protein-only nanoparticles with intrinsic AMP microbicide activity. Using a recombinant version of the GWH1 antimicrobial peptide as building block, these materials show a wide antibacterial activity spectrum in absence of detectable toxicity on mammalian cells. The GWH1-based nanoparticles combine clinically appealing properties of nanoscale materials with full biocompatibility, structural and functional plasticity and biological efficacy exhibited by proteins. Because of the largely implemented biological fabrication of recombinant protein drugs, the protein based platform presented here represents a novel and scalable strategy in antimicrobial drug design, that by solving some of the limitations of AMPs offers a promising alternative to conventional antibiotics. Statement of Significance The low molecular weight antimicrobial peptide GWH1 has been engineered to oligomerize as self assembling protein-only nanoparticles of around 50 nm. In this form, the peptide exhibits potent and broad antibacterial activities against both Gram-positive and Gram-negative bacteria, without any harmful effect over mammalian cells. As a solid proof-of-concept, this finding strongly supports the design and biofabrication of nanoscale antimicrobial materials with in-built functionalities. The protein-based homogeneous composition offer advantages over alternative materials explored as antimicrobial agents, regarding biocompatibility, biodegradability and environmental suitability. Beyond the described prototype, this transversal engineering concept has wide applicability in the design of novel nanomedicines for advanced treatments of bacterial infections. (C) 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Functionalization of thin and stretchable polymer layers by nano- and micro-patterning of nanoparticles is a very promising field of research that can lead to many different applications in biology and nanotechnology. In this work, we present a new procedure to self-assemble semiconductor quantum dots (QDs) nanoparticles by a simple fabrication process on a freestanding flexible PolyDiMethylSiloxane (PDMS) membrane. We used a Periodically Poled Lithium Niobate (PPLN) crystal to imprint a micrometrical pattern on the PDMS membrane that drives the QDs self-structuring on its surface. This process allows patterning QDs with different wavelength emissions in a single step in order to tune the overall emission spectrum of the composite, tuning the QDs mixing ratio. (C) 2016 Elsevier B.V. All rights reserved.

One of the most powerful strategies for the preparation of nanotubes is based on the stacking of flat-shaped cyclic peptide components. This strategy allows precise control of the nanotube internal diameter, the external properties and, more recently, the structural characterisitics of the internal cavity. The recent advances in these technologies and the applications of the resulting materials are described This work was supported by the Spanish Agencia Estatal de Investigación (AEI) and the ERDF (CTQ2013‐43264‐R and CTQ2016‐78423‐R), and by the Xunta de Galicia and the ERDF (EM2014/011 and Centro singular de investigación de Galicia accreditation 2016‐2019, ED431G/09). N. R.‐V. thanks Mineco and the Gil Davila Foundation for her FPU contract and fellowship, respectively. We also thank the ORFEO‐CINCA network and Mineco (CTQ2016‐81797‐REDC) NON

DNA sensors were assembled by consecutive deposition of thiacalix[4]arenes bearing oligolactic fragments, poly(ethylene imine), and DNA onto the glassy carbon electrode. The assembling of the layers was monitored with scanning electron microscopy, cyclic voltammetry and electrochemical impedance spectroscopy. The configuration of the thiacalix[4]arene core determined self-assembling of the polymeric species to the nano/micro particles with a size of 70&ndash, 350 nm. Depending on the granulation, the coatings show the accumulation of a variety of DNA quantities, charges, and internal pore volumes. These parameters were used to optimize the DNA sensors based on these coatings. Thus, doxorubicin was determined to have limits of detection of 0.01 nM (cone configuration), 0.05 nM (partial cone configuration), and 0.10 nM (1,3-alternate configuration of the macrocycle core). Substitution of native DNA with aptamer specific to aflatoxin M1 resulted in the detection of the toxin in the range of 20 to 200 ng/L (limit of detection 5 ng/L). The aptasensor was tested in spiked milk samples and showed a recovery of 80 and 85% for 20 and 50 ng/L of the aflatoxin M1, respectively.

Gold nanoparticles (AuNPs) made from self-assembling peptides have been used in many research fields and attracted a great deal of attention due to their high stability, biocompatibility and functionality. However, existing preparation methods for peptide-coated AuNPs are post-synthesis processes, which are complicated and time consuming. Therefore, a one-step preparation method for peptide-coated AuNPs is proposed here. The AuNPs obtained by this method exhibit good stability. Importantly, peptide-coated AuNPs with precise different sizes can be prepared by this method through pH control of reducing reagent tyrosine in range of 10.0~12.7. Thus, the one-step preparation method proposed here provides a significant tool for the research in different fields concerning NP size, stability and biocompatibility.

Extremely stable and biocompatible 3D magnetically responsive photonic crystals (MRPCs) are successfully prepared in aqueous solution. Classic hydrothermal synthesis was applied for preparation of the Fe3O4@C core. Modified Stober method was then employed for synthesis of the different size of Fe3O4@C@SiO2. Unlike the traditional magnetic nanoparticles, the highly negative charged superparamagnetic nanospheres (SMNs), i.e., the double-shell structure Fe3O4@C@SiO2 are capable of rapidly self-assembling into 3D MRPCs with full visible and various colors that can be periodically and reversibly tuned under different kinds of external magnetic fields (EMFs) within 1 s. The assembling behavior and mechanism of the 3D MRPCs under EMF were monitored and analyzed. The preparation is simple and the size of the SMN is easily controllable by adjusting the amount of catalyst. Compared with the previous works, the synthesized 3D MRPCs are hydrophilic, and exhibit extremely high stability after 6-month storage. To conclude, our study provides an effective two-step strategy for fabrication of biocompatible 3D MRPCs and it reveals great potentials in biological fields.

By the appropriate selection of functional peptides and proper accommodation sites, we have generated a set of multifunctional proteins that combine selectivity for CXCR4(+) cell binding and relevant endosomal escape capabilities linked to the viral peptide HA2. In particular, the construct T22-GFP-HA2-H6 forms nanoparticles that upon administration in mouse models of human, CXCR4(+) colorectal cancer, accumulates in primary tumor at levels significantly higher than the parental T22-GFP-H6 HA2-lacking version. The in vivo application of a CXCR4 antagonist has confirmed the prevalence of the CXCR4(+) tumor tissue selectivity over unspecific cell penetration, upon systemic administration of the material. Such specificity is combined with improved endosomal escape, what overall results in a precise and highly efficient tumor biodistribution. These data strongly support the functional recruitment as a convenient approach to generate protein materials for clinical applications. More precisely, they also support the unexpected concept that enhancing the unspecific membrane activity of a protein material does not necessarily compromise, but it can even improve, the selective cell targeting offered by an accompanying functional module. Statement of Significance We have shown here that the combination of cell-penetrating and tumor cell-targeting peptides dramatically enhances precise tumor accumulation of protein-only nanoparticles intended for selective drug delivery, in mouse models of human colorectal cancer. This fact is a step forward for the rational design of multifunctional protein nanomaterials for improved cancer therapies. (C) 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

In this study, self-assembling Soluplus&reg, micelles were examined for inherent properties. Through calorimetric analysis, the critical micelle concentration (CMC) could be determined at 25 and 37 &deg, C, and the influence of three media (Milli-Q water, phosphate-buffered saline (PBS) with a pH of 7.4 and 0.1 M HCl) on the lower critical solution temperature (LCST) was detected. Furthermore, the solubilisation of a poorly soluble drug, furosemide, into the Soluplus&reg, micelles was studied. The concentration-dependent properties of the micellar system were assessed through an examination of the micellar size, polydispersity, morphology, viscosity and solubilising properties, which were all found to be affected by the concentration, but temperature, pH and the composition of the test medium were also found to have an effect. Homogeneity in the estimated micellar size and morphology was shown for monophasic micelle dispersions in lower concentrations and with a shift towards more complex structures or aggregates in higher concentrations. The micelles were further investigated in terms of drug release and biocompatibility with mucus-producing HT29-MTX cells, where no biocompatibility issues were found. In this research, the implications for oral drug delivery are discussed and valuable preformulation information is provided on the micellar properties of a Soluplus&reg, drug system in a liquid or semi-solid form.

The membrane pore-forming activities of the antimicrobial peptide GWH1 have been evaluated in combination with the CXCR4-binding properties of the peptide T22, in self-assembling protein nanoparticles with high clinical potential. The resulting materials, of 25 nm in size and with regular morphologies, show a dramatically improved cell penetrability into CXCR4+ cells (more than 10-fold) and enhanced endosomal escape (the lysosomal degradation dropping from 90% to 50%), when compared with equivalent protein nanoparticles lacking GWH1. These data reveal that GWH1 retains its potent membrane activity in form of nanostructured protein complexes. On the other hand, the specificity of T22 in the CXCR4 receptor binding is subsequently minimized but, unexpectedly, not abolished by the presence of the antimicrobial peptide. The functional combination T22-GWH1 results in 30% of the nanoparticles entering cells via CXCR4 while also exploiting pore-based uptake. Such functional materials are capable to selectively deliver highly potent cytotoxic drugs upon chemical conjugation, promoting CXCR4-dependent cell death. These data support the further development of GWH1-empowered cell-targeted proteins as nanoscale drug carriers for precision medicines. This is a very promising approach to overcome lysosomal degradation of protein nanostructured materials with therapeutic value. Fil: Serna, Naroa. Universitat Autònoma de Barcelona; España. CIBER de Bioingeniería, Biomateriales y Nanomedicina; España Fil: Sanchez, Julieta Maria. CIBER de Bioingeniería, Biomateriales y Nanomedicina; España. Universitat Autònoma de Barcelona; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Química. Cátedra de Química Biológica; Argentina Fil: Unzueta, Ugutz. CIBER de Bioingeniería, Biomateriales y Nanomedicina; España. Hospital de la Santa Creu i Sant Pau; España Fil: Sánchez-Garcia, Laura. Universitat Autònoma de Barcelona; España. CIBER de Bioingeniería, Biomateriales y Nanomedicina; España Fil: Sánchez-Chardi, Alejandro. Universitat Autònoma de Barcelona; España Fil: Mangues, Ramón. Hospital de la Santa Creu i Sant Pau, Barcelona; España. CIBER de Bioingeniería, Biomateriales y Nanomedicina; España Fil: Vázquez, Esther. Universitat Autònoma de Barcelona; España. CIBER de Bioingeniería, Biomateriales y Nanomedicina; España Fil: Villaverde Corrales, Antonio. Universitat Autònoma de Barcelona; España. CIBER de Bioingeniería, Biomateriales y Nanomedicina; España

Peptide drugs hold great promise for the treatment of infectious diseases thanks to their novel mechanisms of action, low toxicity, high specificity, and ease of synthesis and modification. Naturally developing self-assembly in nature has inspired remarkable interest in self-assembly of peptides to functional nanomaterials. As a matter of fact, their structural, mechanical, and functional advantages, plus their high bio-compatibility and bio-degradability make them excellent candidates for facilitating biomedical applications. This review focuses on the self-assembly of peptides for the fabrication of antibacterial nanomaterials holding great interest for substituting antibiotics, with emphasis on strategies to achieve nano-architectures of self-assembly. The antibacterial activities achieved by these nanomaterials are also described.

Summary Alarming situation of toxic substances such as benzene and its analogs in the environment and workplaces, making it important to monitor these chemicals and their metabolites in order to evaluate risk hazards and potential problems caused by exposure to toxic compounds. Benzene is omnipresent in usage across industries. International Agency for Research on Cancer (IARC) which is a part of World Health Organization (WHO) has classified Benzene as a human carcinogen. trans-trans Muconic acid (ttMA) is the most important biomarker of benzene for biomonitoring of its low level exposure. In this paper the sensing ability of polyaniline (PANI) to ttMA is investigated for development of cheap, portable and effective electrochemical biosensor. To take this ahead for biosensor device application, successful self-assembling of PANI nanofibers of 40–70 nm range on SS 304 working electrode was achieved. Fourier transform infrared spectroscopy and X-ray diffraction was used to characterize the chemical structure of PANI. Morphology of sample was observed by field emission gun scanning electron microscopy (FEG-SEM). The detection potential of ttMA in phosphate buffer solution of pH 5.8 acting as a supporting electrolyte was found to be at 0.26 V by linear sweep voltammetry.

Nanoscale magnetic materials are the basis of emerging technologies to develop novel magnetoelectronic devices. Self-assembly of polystyrene nanospheres is here used to generate 2D hexagonal dot arrays on Fe50Pd50 thin films. This simple technique allows a wide-area patterning of a magnetic thin film. The role of disorder on functional magnetic properties with respect to conventional lithographic techniques is studied. Structural and magnetic characteristics have been investigated in arrays having different geometry (i.e. dot diameters, inter-dot distances and thickness). The interplay among microstructure and magnetization reversal is discussed. Magnetic measurements reveal a vortex domain configuration in all as-prepared films. The original domain structure changes drastically upon thermal annealing performed to promote the transformation of disordered A1 phase into the ordered, tetragonal L10 phase. First-order reversal magnetization curves have been measured to rule out the role of magnetic interaction among crystalline phases characterized by different magnetic coercivity.

(Arginine-alanine-aspartic acid-alanine)4 ((RADA)4) nanoscaffolds are excellent candidates for use as peptide delivery vehicles: they are relatively easy to synthesize with custom bio-functionality, and assemble in situ to allow a focal point of release. This enables (RADA)4 to be utilized in multiple release strategies by embedding a variety of bioactive molecules in an all-in-one &ldquo, construct&rdquo, One novel strategy focuses on the local, on-demand release of peptides triggered via proteolysis of tethered peptide sequences. However, the spatial-temporal morphology of self-assembling nanoscaffolds may greatly influence the ability of enzymes to both diffuse into as well as actively cleave substrates. Fine structure and its impact on the overall effect on peptide release is poorly understood. In addition, fractal networks observed in nanoscaffolds are linked to the fractal nature of diffusion in these systems. Therefore, matrix morphology and fractal dimension of virgin (RADA)4 and mixtures of (RADA)4 and matrix metalloproteinase 2 (MMP-2) cleavable substrate modified (RADA)4 were characterized over time. Sites of high (glycine-proline-glutamine-glycine+isoleucine-alanine-serine-glutamine (GPQG+IASQ), CP1) and low (glycine-proline-glutamine-glycine+proline-alanine-glycine-glutamine (GPQG+PAGQ), CP2) cleavage activity were chosen. Fine structure was visualized using transmission electron microscopy. After 2 h of incubation, nanofiber networks showed an established fractal nature, however, nanofibers continued to bundle in all cases as incubation times increased. It was observed that despite extensive nanofiber bundling after 24 h of incubation time, the CP1 and CP2 nanoscaffolds were susceptible to MMP-2 cleavage. The properties of these engineered nanoscaffolds characterized herein illustrate that they are an excellent candidate as an enzymatically initiated peptide delivery platform.

International audience; We describe the synthesis of a fully conjugated donor-acceptor-donor triad (ZnPc-BTD-ZnPc) made of zinc phthalocyanine donor fragments (ZnPc) at both ends of a benzothiadiazole-based central dye (BTD). The molecule exhibits a broad absorption in the whole visible range. The introduction of sterically demanding alkoxy chains to the ZnPc fragments is found to limit the molecular organization to a short-range columnar order and the charge-carrier mobility to moderate values, but provides outstanding solubilities in organic solvents.

Microbial fuel cells (MFCs) are promising devices for sustainable energy production, wastewater treatment and biosensors. Anode materials directly interact with electricigens and accept electrons between cells, playing an important role in determining the performance of MFCs. In this study, a novel carbon nanotubes (CNTs) and polyaniline (PANI) nanocomposite film modified Indium-tin oxide (ITO) anode was fabricated through graft polymerization of PANI after the modification of &gamma, aminopropyltriethoxysilane (APTES) on ITO substrate, which was followed by layer-by-layer (LBL) self-assembling of CNTs and PANI alternatively on its surface. (CNTs/PANI)n/APTES/ITO electrode with low charge transfer resistance showed better electrochemical behavior compared to the bare ITO electrode. Twelve layers of CNTs/PANI decorated ITO electrode with an optimal nanoporous network exhibited superior biocatalytic properties with a maximal current density of 6.98 &micro, A/cm2, which is 26-fold higher than that of conventional ITO electrode in Shewanella loihica PV-4 bioelectrochemical system. MFCs with (CNTs/PANI)12/APTES/ITO as the anode harvested a maximum output power density of 34.51 mW/m2, which is 7.5-fold higher than that of the unmodified ITO electrode. These results demonstrate that (CNTs/PANI)12/APTES/ITO electrode has superior electrochemical and electrocatalytic properties compared to the bare ITO electrode, while the cellular toxicity of CNTs has an effect on the performance of MFC with (CNTs/PANI)n/APTES/ITO electrode.

Cross-linking biomolecules with electroconductive nanostructures through noncovalent interactions can result in modular networks with defined biological functions and physical properties such as electric conductivity and viscoelasticity. Moreover, the resulting matrices can exhibit interesting features caused by the dynamic assembly process, such as self-healing and molecular ordering. In this paper, we present a physical hydrogel system formed by mixing peptide-polyethylene glycol and poly(3,4-ethylenedioxythiophene):polystyrene sulfonate. This combinatorial approach, which uses different modular building blocks, could lead to high tunability on aspects of rheology and electrical impedance. The proposed physical hydrogel system is characterized by both a self-healing ability and injectability. Interestingly, the formation of hydrogels at relatively low concentrations led to a network of closer molecular packing of poly(3,4-ethylenedioxythiophene) nanoparticles, reflected by the enhanced conductivity. The biopolymer system can be used to develop three-dimensional cell cultures with incorporated electric stimuli, as evidenced by its contribution to the survival and proliferation of encapsulated mesenchymal stromal cells and their differentiation upon electrical stimulation.

International audience; Small interfering RNA (siRNA) is emerging as a novel therapeutic for treating various diseases, provided a safe and efficient delivery is available. In particular, specific delivery to target cells is critical for achieving high therapeutic efficacy while reducing toxicity. Amphiphilic dendrimers are emerging as novel promising carriers for siRNA delivery by virtue of the combined multivalent cooperativity of dendrimers with the self-assembling property of lipid vectors. Here, we report a ballistic approach for targeted siRNA delivery to cancer cells using an amphiphilic dendrimer equipped with a dual targeting peptide bearing an RGDK warhead. According to the molecular design, the amphiphilic dendrimer was expected to deliver siRNA effectively, while the aim of the targeting peptide was to home in on tumors via interaction of its warhead with integrin and the neuropilin-1 receptor on cancer cells. Coating the positively charged siRNA/dendrimer delivery complex with the negatively charged segment of the targeting peptide via electrostatic interactions led to small and stable nanoparticles which were able to protect siRNA from degradation while maintaining the accessibility of RGDK for targeting cancer cells and preserving the ability of the siRNA to escape from endosomes. The targeted system had enhanced siRNA delivery, stronger gene silencing, and more potent anticancer activity compared to nontargeted or covalent dendrimer-based systems. In addition, neither acute toxicity nor induced inflammation was observed. Consequently, this delivery system constitutes a promising nonviral vector for targeted delivery and can be further developed to provide RNAi-based personalized medicine against cancer. Our study also gives new perspectives on the use of nanotechnology based on self-assembling dendrimers in various biomedical applications.

Aim: Nanoparticle–cell interactions can promote cell toxicity and stimulate particular behavioral patterns, but cell responses to protein nanomaterials have been poorly studied. Results: By repositioning oligomerization domains in a simple, modular self-assembling protein platform, we have generated closely related but distinguishable homomeric nanoparticles. Composed by building blocks with modular domains arranged in different order, they share amino acid composition. These materials, once exposed to cultured cells, are differentially internalized in absence of toxicity and trigger distinctive cell adaptive responses, monitored by the emission of tubular filopodia and enhanced drug sensitivity. Conclusion: The capability to rapidly modulate such cell responses by conventional protein engineering reveals protein nanoparticles as tuneable, versatile and potent cell stressors for cell-targeted conditioning.

Altres ajuts: we are indebted to CIBER de Bioingeniería, Biomateriales y Nanomedicina (project NANOPROTHER) for funding AV. Also, to Marató de TV3 foundation (TV32013-3930). Marató TV3 (2013-2030) granted to RM, for funding research on targeted, protein-based drug delivery. MTPF received a fellowship from Fundação de Amparo a Pesquisa do Estado de São Paulo, Brazil (2015/20193-3).NS by a predoctoral fellowship from the Government of Navarra and UU received a Sara Borrell postdoctoral fellowship from ISCIII. AV received an Icrea Academia Award. Arginine-rich protein motifs have been described as potent cell-penetrating peptides (CPPs) but also as rather specific ligands of the cell surface chemokine receptor CXCR4, involved in the infection by the human immunodeficiency virus (HIV). Polyarginines are commonly used to functionalize nanoscale vehicles for gene therapy and drug delivery, aimed to enhance cell penetrability of the therapeutic cargo. However, under which conditions these peptides do act as either unspecific or specific ligands is unknown. We have here explored the cell penetrability of differently charged polyarginines in two alternative presentations, namely as unassembled fusion proteins or assembled in multimeric protein nanoparticles. By this, we have observed that arginine-rich peptides switch between receptor-mediated and receptor-independent mechanisms of cell penetration. The relative weight of these activities is determined by the electrostatic charge of the construct and the oligomerization status of the nanoscale material, both regulatable by conventional protein engineering approaches.

Hybrid copolymers constituted by short l-phenylalanine (Phe) blocks (i.e., Phen with n ranging from 2 to 25) and l-lactide blocks of different length are synthesized and characterized. The diblock structure is obtained by ring opening polymerization of lactide using a Phe-oligopeptide as macroinitiator. The length of the poly(l-lactide) (PLLA) block is controlled through the [lactide]/[macroinitiator] ratio. Morphologic studies of such hybrid copolymers indicate that the assembly of PLLA can be controlled by introducing short Phe blocks. Spherulites with both positive and negative birefringence are achieved in melt crystallization as a consequence of different lamellar distributions. Instead, a high variety of structures are detected in solution-crystallized samples. Specifically, lozenge single crystals, flower-like crystals, fibrillar structures, compact spheres, ringed sperulites, dendritic structures, microfibers, and braid-like microstructures are observed. Some of the detected morphologies are characteristic of self-assembled Phe-oligopeptides, suggesting that Phe-blocks play a crucial role in the self-assembly properties., The authors thank MINECO and FEDER (MAT2015-69367-R, MAT2015-69547-R, and CTQ2013-40855-R), the Generalitat de Catalunya (2014SGR188) and Gobierno de Aragoń-FEDER (research group E40). Support for the research of C.A. was received through the prize “ICREA Academia” for excellence in research funded by the Generalitat de Catalunya.

Recent advances in biochemical and biophysical research have been achieved through the employment of microfluidic devices. Microfluidic mixing of therapeutic agents with biomaterials yields systems with finely tuned physical-chemical properties for applications in drug and gene delivery. Here, we investigate the role of preparation technology (microfluidic mixing vs. bulk self-assembly) on the transfection efficiency (TE) and cytotoxicity of multicomponent cationic liposome/DNA complexes (lipoplexes) in live Chinese hamster ovarian (CHO) cells. Decoupling TE and cytotoxicity allowed us to combine them in a unique coherent vision. While bulk self-assembly produces highly efficient and highly toxic MC lipoplexes, microfluidics manufacture leads to less efficient, but less cytotoxic complexes. This discrepancy is ascribed to two main factors controlling lipid-mediated cell transfection, i.e. the lipoplex concentration at the cell surface and the lipoplex arrangement at the nanoscale. Further research is required to optimize microfluidic manufacturing of lipoplexes to obtain highly efficient and not cytotoxic gene delivery systems.

The engineering of protein self-assembling at the nanoscale allows the generation of functional and biocompatible materials, which can be produced by easy biological fabrication. The combination of cationic and histidine-rich stretches in fusion proteins promotes oligomerization as stable protein-only regular nanoparticles that are composed by a moderate number of building blocks. Among other applications, these materials are highly appealing as tools in targeted drug delivery once empowered with peptidic ligands of cell surface receptors. In this context, we have dissected here this simple technological platform regarding the controlled disassembling and reassembling of the composing building blocks. By applying high salt and imidazole in combination, nanoparticles are disassembled in a process that is fully reversible upon removal of the disrupting agents. By taking this approach, we accomplish here the in vitro generation of hybrid nanoparticles formed by heterologous building blocks. This fact demonstrates the capability to generate multifunctional and/or multiparatopic or multispecific materials usable in nanomedical applications.

Soft interfacial materials, such as self-assembled polymer membranes, are gaining increasing interest as biomaterials since they can provide selective barriers and/or controlled affinity interactions important to regulate cellular processes. Herein, we report the design and fabrication of multiscale structured membranes integrating selective molecular functionalities for potential applications in bone regeneration. The membranes were obtained by interfacial self-assembly of miscible aqueous solutions of hyaluronan and multi-domain peptides (MDPs) incorporating distinct biochemical motifs, including mineralizing (EE), integrin-binding (RGDS) and osteogenic (YGFGG) peptide sequences. Circular dichroism and Fourier transform infrared spectroscopy analyses of the MDPs revealed a predominant β-sheet conformation, while transmission electron microscopy (TEM) showed the formation of fibre-like nanostructures with different lengths. Scanning electron microscopy (SEM) of the membranes showed an anisotropic structure and surfaces with different nanotopographies, reflecting the morphological differences observed under TEM. All the membranes were able to promote the deposition of a calcium-phosphate mineral on their surface when incubated in a mineralizing solution. The ability of the MDPs, coated on coverslips or presented within the membranes, to support cell adhesion was investigated using primary adult periosteumderived cells (PDCs) under serum-free conditions. Cells on the membranes lacking RGDS remained round, while in the presence of RGDS they appear to be more elongated and anchored to the membrane. These observations were confirmed by SEM analysis that showed cells attached to the membrane and exhibiting an extended morphology with close interactions with the membrane surface. We anticipate that these molecularly designed interfacial membranes can both provide relevant biochemical signals and structural biomimetic components for stem cell growth and differentiation and ultimately promote bone regeneration., This work was supported by national funds through the Portuguese Foundation for Science and Technology (FCT) under the scope of the project PTDC/CTM-BIO/0814/2012 and by the European Regional Development Fund (ERDF) through the Operational Competitiveness Programme "COMPETE" (FCOMP-01-0124-FEDER-028491). J. Borges and R. P. Pirraco gratefully acknowledge funding support from FCT for postdoctoral (SFRH/BPD/103604/2014) and investigator (IF/00347/2015) grants, respectively. Y. Shi acknowledges China Scholarship Council for her PhD scholarship (no. 201307060020). H. S. Azevedo also acknowledges financial support from the EU-funded project "SuprHApolymers" (PCIG14-GA-2013-631871) and A. Mata acknowledges the European Research Council Starting Grant "STROFUNSCAFF" and the Marie Curie Career Integration Grant "BIOMORPH"., info:eu-repo/semantics/publishedVersion

A bi-component nanostructured system composed by a Co dot array embedded in a Ni80Fe20 antidot matrix has been prepared by means of the self-assembling polystyrene nanospheres lithography technique. Reference samples constituted by the sole Co dots or Ni80Fe20 antidots have also been prepared, in order to compare their properties with those of the bi-component material. The coupling between the two ferromagnetic elements has been studied by means of magnetic and magneto-transport measurements. The Ni80Fe20 matrix turned out to affect the vortex nucleation field of the Co dots, which in turn modifies the magneto-resistance behaviour of the system and its spinwave properties.

Hydrogels based on polysaccharide and protein natural polymers are of great interest in biomedical applications and more specifically for tissue regeneration and drug delivery. Cellulose, chitosan (a chitin derivative), and collagen are probably the most important components since they are the most abundant natural polymers on earth (cellulose and chitin) and in the human body (collagen). Peptides also merit attention because their self-assembling properties mimic the proteins that are present in the extracellular matrix. The present review is mainly focused on explaining the recent advances on hydrogels derived from the indicated polymers or their combinations. Attention has also been paid to the development of hydrogels for innovative biomedical uses. Therefore, smart materials displaying stimuli responsiveness and having shape memory properties are considered. The use of micro- and nanogels for drug delivery applications is also discussed, as well as the high potential of protein-based hydrogels in the production of bioactive matrices with recognition ability (molecular imprinting). Finally, mention is also given to the development of 3D bioprinting technologies.

International audience; Glycerol carbonate is one of the most potentially multifunction glycerol-derived compounds. Glycerol is an important by-product of the oleochemical industry. The oligomerization of glycerol carbonate, assisted by the glycerol, results in the production of polyhydroxylated oligomers rich in linear carbonate groups. The polar moieties of these oligomers (Mw

New low molar mass (M-n similar to 20 kg mol(-1)) polystyrene-b-poly(methyl methacrylate-co-perfluorohexylethyl acrylate) (PS-b-P(MMA-co-FA)) block copolymers were synthesized all consisting of similar to 70 mol% PS block and similar to 30 mol % P(MMA-co-FA) block. The amount of FA counits in the latter block was increased (0.5, 1, 3 and 4 mol%) in order to enhance the incompatibility between the two blocks and to form different self-assembled nanostructures. The block copolymers were thermally annealed by Rapid Thermal Processing (RTP) over wide ranges of temperatures and times. Complementary SEM and AFM analyses evidenced that the introduction of FA counits above a critical content (similar to 2 mol%) drove a self-assembly process through mixed morphologies. These were formed at a distance from the polymer-air interface and consisted of perpendicular cylinders of P(MMA-co-FA) in a PS matrix laying at the substrate- polymer interface, and surmounted PS stripes and PS dots. Modification by low amounts of FA produced block copolymer samples that self-assembled in new, mixed nanostructures, even though they possessed much lower molar masses than those of analogous well established PS-b-PMMA block copolymers.

International audience; Novel thermo-responsive poly(N-isopropylacrylamide)-block-poly(l-lactide)-block-poly(N-isopropylacylamide) (PNIPAAm-b-PLLA-b-PNIPAAm) triblock copolymers were successfully prepared by atom transfer radical polymerization of NIPAAm with Br-PLLA-Br macroinitiator, using a CuCl/tris(2-dimethylaminoethyl) amine (Me6TREN) complex as catalyst at 25 °C in a N,N-dimethylformamide/water mixture. The molecular weight of the copolymers ranges from 18,000 to 38,000 g mol−1, and the dispersity from 1.10 to 1.28. Micelles are formed by self-assembly of copolymers in aqueous medium at room temperature, as evidenced by 1H NMR, dynamic light scattering (DLS) and transmission electron microscopy (TEM). The critical micelle concentration determined by fluorescence spectroscopy ranges from 0.0077 to 0.016 mg mL−1. 1H NMR analysis in selective solvents confirmed the core-shell structure of micelles. The copolymers exhibit a lower critical solution temperature (LCST) between 32.1 and 32.8 °C. The micelles are spherical in shape with a mean diameter between 31.4 and 83.3 nm, as determined by TEM and DLS. When the temperature is raised above the LCST, micelle size increases at high copolymer concentrations due to aggregation. In contrast, at low copolymer concentrations, decrease of micelle size is observed due to collapse of PNIPAAm chains.

© 2016 American Chemical Society. Rice straw cellulose was completely defibrillated via aqueous counter collision (ACC) at a low energy input of 15 kWh/kg, then fractionated by differential centrifugation into four increasing weight fractions of progressively thinner cellulose nanofibrils (CNFs): 6.9% in 80-200 nm, 14.4% in 20-80 nm, 20.3% in 5-20 nm, and 58.4% in less than 5 nm thickness. The 93.1% less than 80 nm or 78.7% less than 20 nm thick CNFs yields were more than double those from wood pulp by other mechanical means but at a lower energy input. The smallest (3.7 nm thick and 5.5 nm wide) CNFs were only a third or less in lateral dimensions than those obatined through ACC processed from wood pulp, bamboo, and microbial cellulose pellicle. The less than 20 nm thick CNFs could self-assemble into continuous submicron (136 nm) wide fibers by freezing and freeze-drying or semitransparent (13-42% optical transmittance) film by ultrafiltration and air-drying with excellent mechanical properties (164 MPa tensile strength, 4 GPa Young's modulus, and 16% strain at break). ACC defibrillated CNFs retained essentially the same chemical and crystalline structures and thermal stability as the original rice straw cellulose and therefore were much more thermally stable than TEMPO oxidized CNFs and sulfuric acid hydrolyzed cellulose nanocrystals from the same rice straw cellulose.

A single chain polypeptide containing the low density lipoprotein receptor (LDLR) ligand Seq-1 with blood-brain barrier (BBB) crossing activity has been successfully modified by conventional genetic engineering to self-assemble into stable protein-only nanoparticles of 30 nm. The nanoparticulate presentation dramatically enhances in vitro, LDLR-dependent cell penetrability compared to the parental monomeric version, but the assembled protein does not show any enhanced brain targeting upon systemic administration. While the presentation of protein drugs in form of nanoparticles is in general advantageous regarding correct biodistribution, this principle might not apply to brain targeting that is hampered by particular bio-physical barriers. Irrespective of this fact, which is highly relevant to the nanomedicine of central nervous system, engineering the cationic character of defined protein stretches is revealed here as a promising and generic approach to promote the controlled oligomerization of biologically active protein species as still functional, regular nanoparticles. (C) 2016 Elsevier Inc. All rights reserved.