A fast and solvent-free protocol to introduce amides and amines onto graphene oxide

Título: A fast and solvent-free protocol to introduce amides and amines onto graphene oxide

Solvent-free functionalisation of graphene oxide with amide and amine groups at room temperature
Stefania Sandoval, Amparo Fuertes, Gerard Tobias
Chemical Communications 55, 81, 12196-12199, 2019
DOI: 10.1039/C9CC05693A

Figure: Ammonolysis at room temperature induces the efficient formation of amine and amide groups (N-functionalization) onto the graphene oxide (GO) surface.

We present a new, simple, fast and energy efficient solvent-free protocol that allows the introduction of amides and amines onto graphene oxide (GO) at room temperature. This approach allows the functionalization of GO even with extremely reduced amounts of ammonia (NH3) gas and greatly expands the derivatisation routes to integrate graphene derivatives into devices and composite materials.

Atomistic insight into nanostructured biomaterials

Título: Atomistic insight into nanostructured biomaterials

Long-lived ionic nano-domains can modulate the stiffness of soft interfaces
William Trewby, Jordi Faraudo, Kislon Voitchovsky
Nanoscale 11, 4376-4384, 2019
DOI: 10.1039/C8NR06339G

Protein-surface interactions at the nanoscale: Atomistic simulations with implicit solvent models
David C. Malaspina, Leonor Perez-Fuentes, Carlos Drummond, Delfi Bastos-Gonzalez, Jordi Faraudo
Current Opinion in Colloid & Interface Science 41, 40-49, 2019
DOI: 10.1016/j.cocis.2018.11.005

Figure: Summary of the systems studied by atomistic MD simulations. Left: different configurations of cations adsorbed onto a lipid membrane linked by hydration water molecules. Center: nanostructures and patterns of adsorbed cations ions over a lipid membrane. Right: example of a protein adsorbed onto an inorganic surface.

Using Supercomputers we perform molecular dynamics simulations of materials at scales of the order of a million of atoms. In this way we obtain unprecedent insight into the way that nanostructuration of biomaterials influence their properties. The examples considered here were how ionic domains modulate the elastic properties of biomembranes or how proteins interact with inorganic nanomaterials.

Bacterial cellulose patches for plant healing

Título: Bacterial cellulose patches for plant healing
Subtítulo: Antibacterial patches of bacterial cellulose and silver nanoparticles protect and heal plant wounds: joint publication between ICMAB and CRAG

Enhancing Localized Pesticide Action through Plant Foliage by Silver-Cellulose Hybrid Patches Alejandro Alonso-Díaz, Jordi Floriach-ClarkJudit FuentesMontserrat CapelladesNúria S. CollAnna Laromaine
ACS Biomater. Sci. Eng. 5 (2), pp 413–419, 2019
DOI: 10.1021/acsbiomaterials.8b01171

Figure: (Left) Tomato plant leaves covered with bacterial cellulose (left), plant cellulose (top) and the silver nanoparticles-bacterial cellulose hybrid patch (bottom) at the site of infection with the bacterial pathogen Pseudomonas syringae pv tomato, causing agent of bacterial speck. (Right) Schematics of the placing of the antibacterial patch on the infected leaves.

Plants, like humans, can also get wounded. These wounds can be caused by several agents and are a breach of the outer protective layers (the skin) of plants, giving open access to many microbial pathogens that can cause severe diseases, resulting in dramatic crop losses for farmers.

Herein we present a material to avoid contamination and heal plant wounds. This solution is based on the use of an environmentally friendly nanocomposite patch made of bacterial cellulose and silver nanoparticles.

Currently, the efficacy and efficiency of the pesticides used to fight crop infections still face many challenges. Seeking to improve them, we have anchored antipathogenic silver nanoparticles, to the bacterial cellulose structure. An advantage of this biopolymer is that its molecular structure is similar to plant cellulose, one of the plant’s main structural components. Moreover, due to its high-water holding capacity, bacterial cellulose has a hydrogel-like consistency, which increases its adherence to the plant leaves. The wound healing properties of bacterial cellulose have already been patented. The hybrid patch avoids runoff loss and rolling down of the nanoparticles, providing a slow and effective release of the pesticide effects from the bacterial cellulose and safety to our environment.

We have demonstrated the positive antibacterial and antifungal properties of these hybrid patches in in vitro assays against Escherichia coli and two agro-economically relevant pathogens: the bacterium Pseudomonas syringae and the fungus Botrytis cinerea. In addition, in vivo infection inhibition was proved in two different plants (Nicotiana benthamiana and tomato plant leaves).

Biofunctionalized substrates for high-throughput cell motility studies

Título: Biofunctionalized substrates for high-throughput cell motility studies
Subtítulo: High-throughput cell motility studies on substrates biofunctionalized with protein nanoparticles with eighty areas presenting diferent structural and compositional characteristics

High-Throughput Cell Motility Studies on Surface-Bound Protein Nanoparticles with Diverse Structural and Compositional Characteristics
Witold I. Tatkiewicz, Joaquin Seras-Franzoso, Elena Garcia-Fruitos, Esther Vazquez, Adriana R. Kyvik, Nora Ventosa, Judith Guasch, Antonio Villaverde, Jaume Veciana, Imma Ratera
ACS Biomaterials Science & Engineering 5, 5470-5480, 2019
DOI: 10.1021/acsbiomaterials.9b01085

Figure: Scheme of 9 different areas ilustrating the inputs used for the high-throughput and the resulting cell motiliy outputs studied

Surface-bound gradients of protein nanoparticles (pNPs) consisting of the green fluorescence protein (GFP) have been recently shown to influence cell motility (ACS Appl. Mater. Interfaces, 10,25779, 2018). Encouraged by the latter results, which were based only on physical cues (i.e., topography, geometry, and roughness), here we have studied the effects of fibroblast growth factor (FGF) based pNPs that introduce a biochemical activity to the substrate for promoting cell migration.

Eighty areas with different structural and compositional characteristics made of pNPs formed by FGF-pNPs were simultaneously patterned on a glass surface using a recently reported device based on an evaporation-assisted method that relies on the coffee-drop effect. The resulting surface enabled to perform a high-throughput study of the motility of NIH-3T3 fibroblasts under the different conditions including gradient steepness, particle concentrations, and area widths of patterned FGF-pNPs, in a fast way reducing the time and resources needed, as well as the batch to- batch variability that sometimes occurs in the pNP production. With the resulting patterned surface, we studied in the same experiment the influence of the following factors: (A) constant vs gradient concentrations of pNPs, (B) the steepness of pNP gradients, (C) the different absolute concentrations of pNPs, and (D) the impact of broad vs narrow paths (i.e., cell movement constraining on cell motility).

For the data analysis we have used a methodology that includes “heat maps”. From this analysis, we observed that gradients of concentrations of surface-bound FGF-pNPs stimulate the total cell movement but do not affect the total net distances traveled by cells. Moreover, cells tend to move toward an optimal intermediate FGF-pNP concentration. Additionally, a higher motility was obtained when cells were deposited on narrow and highly concentrated areas with pNPs demonstrating that FGF-pNPs can be therefore used to enhance and guide cell migration, confirming that the decoration of surfaces with such pNPs is a promising platform for regenerative medicine and tissue engineering.

Combining magnetic nanoparticles and icosahedral boron clusters in biocompatible inorganic nanohybrids for cancer therapy

Título: Combining magnetic nanoparticles and icosahedral boron clusters in biocompatible inorganic nanohybrids for cancer therapy

Combining magnetic nanoparticles and icosahedral boron clusters in biocompatible inorganic nanohybrids for cancer therapy
Oleshkevich, Elena; Morancho, Anna; Saha, Arpita; Galenkamp, Koen M. O.; Grayston, Alba; Crich, Simonetta Geninatti; Alberti, Diego; Protti, Nicoletta; Comella, Joan X.; Teixidor, Francesc; Rosell, Anna; Vinas, Clara
Nanomedicine: Nanotechnology, Biology, and Medicine 20 (2019) 101986
DOI: 10.1016/j.nano.2019.03.008

Figure: Schematic representation of the bifunctional magnetic nanoparticles (1-MNPs) and a TEM image of a A172 glioblastoma cell showing the presence of 1-MNPs into the cytoplasm with a larger load.

Cancer is among the leading causes of death worldwide. According to International Agency for Research on Cancer, cancer burden rises to 18.1 million new cases and 9.6 million deaths in 2018. Most of the FDA approved anticancer drugs are purely organic molecules. The successful introduction of cisplatin as an anticancer drug in the early 1980’s opened the possibility to investigate the potential applications of organometallic complexes in medicine. Boron and carbon are the elements that have the property to build molecules of unlimited size by covalent self-bonding. Largely, the white solid twelve-vertex C2B10H12 carboranes, rank among the most chemical and biological stable molecular compounds known, which display many particular characteristics that do not find a parallel in their organic counterparts. Current chemotherapy cancer treatments not only kill both cancer and healthy cells but also frequently produces drug resistance in human patients that makes treatment failure. In order to overcome this situation, more effective and selective treatments are necessary. Boron Neutron Capture Therapy (BNCT), based on the large capture neutrons surface of 10B atoms, is a promising binary therapy for the treatment of cancer, because malignant cells can be selectively targeted and destroyed.

Following our research based on the development of a new hybrid compounds’ families that offering the possibility of dual action (chemiotherapy + radiotherapy) may result into significant clinical benefits. The reported bifunctional nanoparticles (1-MNPs) combine magnetic core and icosahedral boron-clusters to develop new bimodal cancer treatment (thermoterapy + BNCT) with the aim to obtain the best therapeutic effect using the lowest doses and therefore avoiding unwanted organism toxicity and side effects suffered by the patient. The cellular uptake and toxicity profile of 1-MNPs from culture media by human brain endothelial cells (hCMEC/D3) and glioblastoma multiform A172 cell line were demonstrated as well as colloidal stability studies in different culture media and temperatures. Importantly, thermal neutrons irradiation in BNCT reduced by 2.5 the number of cultured glioblastoma cells after 1-MNP treatment, and the systemic administration of 1-MNPs in mice was well tolerated with no major signs of toxicity.

Electroactive conducting electrode materials for neural growth

Título: Electroactive conducting electrode materials for neural growth

Electric Field Gradients and Bipolar Electrochemistry effects on Neural Growth. A finite element study on inmersed electroactive conducting electrode materials
Llibertat Abad, Ann M. Rajnicek, Nieves Casañ-Pastor
Electrochimica Acta 317 (2019) 102-111
DOI: 10.1016/j.electacta.2019.05.149

Figure: Induced dipoles electrochemistry affecting neural growth.

Electric dipoles induced on conducting materials within electrochemical cells, modify neural behaviour in substantial ways. This work evaluates the field gradients and intercalation processes that occur at the poles of the unconnected mixed conducting material serving as neural growth support, and that eventually favour direction and speed of neural growth. Remote control of electrostimulation processes in the neural system may be devised and lower impedance energy storage systems demonstrated.

From nanoparticles to a mesoporous material

Título: From nanoparticles to a mesoporous material

Controlled Self‐Assembly of Mesoporous CuO Networks Guided by Organic Interlinking
José Antonio Ayllón, Julio Fraile, Concepción Domingo
Particle and Particle Systems Characterization 36(3):1800453, 2019
DOI: 10.1002/ppsc.201800453

Figure: Scheme showing the process to transform a nanoparticle dispersion into a mesoporous material using a polytopic linker.

A simple way of transforming a colloidal dispersion of nanoparticles into a mesoporous solid with noticeable thermal stability is described. The strategy consists into the partial replacement of the shell of monotopic capping ligands, with proper functionalization to impart good dispersability, by rigid polytopic ligands that favor a controlled aggregation.

Multiwalled carbon nanocapsules for cancer diagnosis and therapy

Título: Multiwalled carbon nanocapsules for cancer diagnosis and therapy
Subtítulo: A simple and versatile one-step filling and end-closing of multi-walled carbon nanotubes with potential application in cancer diagnosis and therapy.

Non-cytotoxic carbon nanocapsules synthesized via one-pot filling and end closing of multi-walled carbon nanotubes
Markus Martincic, Sandra Vranic, Elzbieta Pach, Stefania Sandoval, Belén Ballesteros, Kostas Kostarelos, Gerard Tobias
Carbon 141, 782-793, 2019
DOI: 10.1016/j.carbon.2018.10.006

Figure: (a) Schematic representation of the synthesis of multiwalled carbon nanocapsules (closed-ended filled carbon nanotubes), (b) BET surface area of empty MWCNTs annealed at different temperatures and (c) flow cytometry using PI/Annexin V staining (alive cells are represented in P18 region, early apoptotic in P19, late apoptotic and/or necrotic cells in P17 and necrotic cells in P16.)


Carbon nanotubes (CNTs) have remarkable properties with applications in a wide range of fields. Moreover, the presence of an inner cavity expands their versatility, allowing their endohedral modification. Among the large variety of materials that can be filled in their interior, the encapsulation of biomedically relevant payloads inside CNTs has taken a great deal of attention. CNTs not only offer protection to the encapsulated cargo from the biological milieu, but also can be externally modified by the attachment of selected biomolecules that can provide an increase in the biocompatibility and selectivity of the material.

Filling of CNTs is typically performed using an excess of the guest material and a large amount of the filler remains external to the walls after synthesis. The non-encapsulated compounds can induce negative side effects when employed in the biomedical field. For this reason, a subsequent washing protocol for the selective elimination of the external material, while preserving the inner compound, must be performed. In this context, we have reported a fast and simple method that allows the formation of a wide variety of multiwalled carbon nanocapsules (closed-ended filled CNTs), clean from external, non-encapsulated material. The proposed methodology consists in thermally annealing open-ended MWCNTs in the presence of a chosen payload at temperatures ranged between 1000 °C and 1200 °C, which leads to their simultaneous filling and end-closing. Once the MWCNTs are filled, the non-encapsulated compounds can be easily removed in a fast manner. This approach has demonstrated to be highly versatile, since several biomedically relevant compounds have been sealed in the cavities of CNTs. In vitro studies of both empty and filled MWCNTs showed that nanocapsules did not induce cellular death after being internalized by cells.

Photoluminescent boron-based materials for bioimaging and cancer treatment

Título: Photoluminescent boron-based materials for bioimaging and cancer treatment
Subtítulo: We have developed a set of photoluminescence boron-containing molecular materials that exhibit blue light emission with extraordinary high quantum efficiency (around 100 %), making them excellent candidates for optical devices and bioimaging probes. Moreover, due to the high boron content of these materials, they could be useful for BNCT cancer therapy.

Efficient blue light emitting materials based on m-carborane-anthracene dyads. Structure, photophysics and bioimaging studies
Mahdi Chaari, Zsolt Kelemen, Duane Choquesillo-Lazarte, Nerea Gaztelumendi, Francesc Teixidor, Clara Viñas, Carme Nogués,* Rosario Núñez*. Biomaterials Science, 7, 5324, 2019
DOI: 10.1039/C9BM00903E

Figure: Fluorescence intensity emitted by cells incubated for 4 h with 10 µM of diiodinated antracene-m-carborane. Image obtained with the confocal laser scanning microscope.

The development of photoluminescent boron cluster-based organic p-conjugated systems has attracted huge interest as active materials in (opto)electronic devices, solar cells, biological sensors and fluorescence bioimaging. Anthracene derivatives are molecules with excellent luminescence properties, whereas carborane clusters (C2B10H12) are fascinating chemical species with unique structural and electronic properties, as well as low toxicity in biological systmes.  In carborane-containing fluorophores, the fluorescence efficiency can be tailored by the cluster isomer and the substituent at the cluster atom (Cc). 

We have synthesized three m-carborane-anthracenyl dyads, containing 0, 1 or 2 iodo groups at Bc atoms. They exhibit exceptional blue emission properties with high quantum yields (around 100 %) in solution, confirming that linking m-carborane to a fluorophore produces a significant enhancement of the emission efficiency in the target compounds. Notably, these dyads exhibit moderate fluorescence in aggregate state (between 19–23 %), pointing out that they are extremely good emitters in solution, while maintaining the emission properties in solid state. None of them shows cytotoxicity for HeLa cells. Confocal microscopy studies confirm that all compounds are internalised by cells via endocytosis, being the di-iodinated compound the best-internalised by cells. This suggest that the presence of iodo lead to a higher lipophilicity facilitating an efficient transport across the plasma membrane and a better cellular uptake. This di-iodinated dyad is an excellent fluorescent dye for bioimaging studies in fixed cells, and due to the high boron content and exceptional cellular uptake, a potential anticancer agent for Boron Neutron Cancer Therapy (BNCT).

Self-assembled metallacarborane corona on a protein molecule

Título: Self-assembled metallacarborane corona on a protein molecule

Dual Binding Mode of Metallacarborane Produces a Robust Shield on Proteins
Isabel Fuentes, Jordi Pujols, Clara Viñas, Salvador Ventura, Francesc Teixidor
Chem. Eur. J. 25, 12820-12829, 2019
DOI: 10.1002/chem.201902796

Figure: Bovine Serum Albumin (BSA)’s volume from Dynamic Light Scattering (DLS) and the representations of Na[COSAN] covering a single BSA core molecule (a) first, (b) second, (c) third and (d) fourth layers.

Metallacarboranes like [Co(C2B9H11)2]-, which self-assemble, have the property to strongly interact with amines. Therefore, they should be able to interact with certain aminoacids that are present in proteins. This paper reports on the stable coating of Bovine Serum Albumin (BSA) by the metallacarborane [Co(C2B9H11)2]- through the anchoring with the amino residues and fulfilling the complementary surface by self-assembling. Many of the protein’s properties are preserved even at higher temperatures than denaturalization.

The atomistic origin of the peculiar amphiphilic behavior of cellulose

Título: The atomistic origin of the peculiar amphiphilic behavior of cellulose

Molecular insight into the wetting behavior and amphiphilic character of cellulose nanocrystals
David C. Malaspina and Jordi Faraudo
Advances in Colloid and Interface Science 267, 15–25, 2019
DOI: 10.1016/j.cis.2019.02.003

Figure: Summary of the systems studied by atomistic MD simulations. Center: scheme of the cellolose crystal structures considered in this work. Top: snapshots from the simulations of celloluse surfaces in contact with  different molecules in water (carbonate ion, EGF protein and tetraphenil borate ion). Bottom: snapshots from the wetting simulations of cellulose with droplets of different solvents (water and organic solvent (tetradecane)). Movies of the simulations can be seen in the SoftMatter Youtube channel: https://www.youtube.com/playlist?list=PLWhDHF4i-Is0c407wNLOEhH4aiEHFPLOb

Cellulose (the most abundant biopolymer in Earth) shows a puzzling behavior in its interaction with solvents. It has a strong H-bonding capacity, typical of hydrophilic molecules, but it is insoluble in water. There are also controvertial claims of the presence of hydrophobic interactions in cellulose and possible amphiphilic behavior. This question was clarified using extensive atomistic molecular dynamics simulations of different crystal surfaces of cellulose and different solvents (water and organic solvents) and different molecules (small hydrophilic or hydrophobic solutes, proteins with exposed aminoacids of hydrophilic and hydrophobic character).

Our results show that crystalline cellulose have the remarkable property of being simultaneously hydrophilic and lipophilic. In our work this behavior is directly linked to both the molecular structure and the supramolecular organization of crystalline cellulose.

Towards theranostic albumin-iron oxide nanocages

Título: Towards theranostic albumin-iron oxide nanocages

Insights into preformed HSA corona on iron oxide nanoparticles: structure, effect of particle size, impact on MRI efficiency and metabolization
Carlos Moya, Remei Escudero, David C. Malaspina, Maria de la Mata, Jesús Hernández-Saz, Jordi Faraudo, Anna Roig
ACS Appl. Bio Mater. 2, 7, 3084–3094, 2019
DOI: 10.1021/acsabm.9b00386

Figure: Excellent accordance between the values obtained from spectroscopy studies and results from molecular dynamics simulation: A) the number of proteins units forming a monolayer of human serum albumin (HSA) corona on the surface of iron oxide nanoparticles of different sizes. HSA corona enhances particle integrity and stability in biological media:  B) The hydrodynamic diameter of HSA-nanoparticles is stable up to 25 hours in gastric-like conditions. C) MRI performance of the HSA-nanoparticles is unaltered after their incubation in PBS for 90 days.

The spontaneous protein corona formed on nanoparticles in biological media can be detrimental for their intended biomedical uses. Herein we present a universal route to preform a monolayer of human albumin onto iron oxide nanoparticles guided by molecular dynamic simulations. This well-defined albumin corona acts as a bio-shield against the rapid acidic-dissolution of the iron oxide cores, it increases their colloidal dispersability in PBS (phosphate-buffered saline) and it does not interfere with the nanoparticles' performance as magnetic resonance imaging (T2-MRI) contrast agent. Theranostic drug delivery albumin-nanocages attained by partial dissolution of the inorganic core are proposed as the follow-up of this work.

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