Incorporation of Molecular Nanoparticles Inside Proteins: The Trojan Horse Approach in Theranostics

CONSPECTUS: Molecular nanoparticles, MNPs, characterized by well-defined chemical formulas, structures, and sizes can interact with a variety of proteins. Fullerenes, carboranes, and gold nanoclusters well represent the diversity of MNPs properties available in nanoscience. They can have diameters smaller than 1.5 nm, be hydrophilic or hydrophobic, and can use a paraphernalia of means to establish local and global interactions with the amino acidic residues of proteins. Proteins, endowed as they are with an assortment of pockets, crevices, and gaps are natural supramolecular hosts to incorporate/hide/transport MNPs directly in water with a facile and "green" approach.This Account identifies and discusses the rules that govern the interactions and binding between MNPs and proteins. Fullerenes are composed solely by carbon atoms arranged to form hollow polyhedra. Hydrophobic interactions occur between aliphatic residues and the fullerene surface. The amino acids most effectively interacting with fullerenes are aromatic residues that establish p-p stacking interactions with the cage. Amphiphilic and charged residues produce also cation-p, anion-p, and surfactant-like interactions with the cages.Carboranes are composed of boron, carbon, and hydrogen atoms, also arranged to form cages. They are hydrophobic with unusual properties originating from the presence of boron atoms. Hydride-like hydrogens bound to the boron atoms govern carborane chemistry. These negatively charged hydrogens do not participate in classic hydrogen bonding with water and promote hydrophobic interactions with proteins. On the contrary, the electronegativity of these hydrogens drives the formation of unconventional dihydrogen bonds with the acidic hydrogen atoms of positively charged amino acid. Carboranes also establish C-H center dot center dot center dot p and B-H center dot center dot center dot p interactions with aromatic residues.Gold nanoclusters, AuNCs, are synthesizable with atomically precise stoichiometry. Amino acid residues with sulfur atoms or with nitrogen-containing heterocycles are the strongest Au binders. The proteins can act as supramolecular hosts but also as templates for the synthesis of AuNCs directly inside the protein core. Of the pristine amino acids, tryptophan, tyrosine, phenylalanine, and aspartic acid are the most efficient reducing groups. In a peptide sequence, the best Au-reducing moieties are obtained by nitrogencontaining residue such as glutamine, asparagine, arginine, and lysine. The investigation of the interactions between AuNCs and proteins therefore adds further complexity with respect to that of fullerenes and carboranes. The selection of the host proteins should consider that they will have to contain active sites for metal ion accumulation and ion reduction where AuNC can form and stabilize. This Account further discusses the hybridization of MNPs with proteins in view of creating innovative multifunctional theranostic platforms where the role of proteins is akin to that of "Trojan Horses" since they can (i) hide the MNPs, (ii) control their cellular uptake, (iii) drive their crossing of physiological barriers, and (iv) ultimately govern their biological fate

Tramas y sistemas de repetición

En base a la investigación sobre tramas y sistemas de repetición se toma una trama geométrica particular y así se desarrolla una serie de diagramas que delimitan el proyecto Arquitectónico. Este último se ubica en el Delta del río Paraná y contiene como programa un hotel

Two Approaches in Computer Simulation of the MFM-images

Two approaches to the interpretation of the data of magnetic force microscopy are considered. The first approach involves the reconstruction of the magnetization distribution in the researched samples on the base of an assumption about the magnetic state and the subsequent numerical magnetic force microscopy experiment. The second is related to an experimental data processing

Clinical Influences in the Multidisciplinary Management of Small Renal Masses at a Tertiary Referral Center

Introduction We designed a multidisciplinary Small Renal Mass Center to help patients decide among treatment options and individualize therapy for small renal masses. In this model physicians and support staff from multiple specialties work as a team to evaluate and devise a treatment plan for patients at the same organized visit. Methods We retrospectively reviewed the records of 263 patients seen from 2009 to 2014. Monitored patient characteristics included age, Charlson comorbidity index, body mass index, nephrometry score, tumor size and estimated glomerular filtration rate. Univariate and multivariate analyses were performed to identify patient characteristics associated with each treatment choice. Results Of the cohort 88 patients elected active surveillance, 64 underwent ablation and 111 were treated with surgery, including partial and radical nephrectomy in 74 and 37, respectively. There were significant associations between treatment modality and age, Charlson comorbidity index, tumor size and estimated glomerular filtration rate. Mean patient age at presentation was 61.1 years. Patients with a high Charlson comorbidity index score (greater than 5) or a decreased estimated glomerular filtration rate (less than 60 ml/minute/1.73 m2) were more likely to undergo active surveillance (41.6% and 35%) and ablative therapy (29.6% and 34%) vs partial nephrectomy (10.6% and 9%, respectively, each p \u3c0.001). On multivariable analysis age, tumor size and estimated glomerular filtration rate remained significantly associated with modality after adjustment for all other factors (each p \u3c0.001). Conclusions The Small Renal Mass Center enables patients to assess the various treatment modalities for a small renal mass in a single setting. By providing simultaneous access to the various specialists it provides an invaluable opportunity for informed patient decision making. © 2016 American Urological Association Education and Research, Inc

Fullerenes against COVID-19: Repurposing C60 and C70 to Clog the Active Site of SARS-CoV-2 Protease

The persistency of COVID-19 in the world and the continuous rise of its variants demand new treatments to complement vaccines. Computational chemistry can assist in the identification of moieties able to lead to new drugs to fight the disease. Fullerenes and carbon nanomaterials can interact with proteins and are considered promising antiviral agents. Here, we propose the possibility to repurpose fullerenes to clog the active site of the SARS-CoV-2 protease, M-pro. Through the use of docking, molecular dynamics, and energy decomposition techniques, it is shown that C-60 has a substantial binding energy to the main protease of the SARS-CoV-2 virus, M-pro, higher than masitinib, a known inhibitor of the protein. Furthermore, we suggest the use of C-70 as an innovative scaffold for the inhibition of SARS-CoV-2 M-pro. At odds with masitinib, both C-60 and C-70 interact more strongly with SARS-CoV-2 M-pro when different protonation states of the catalytic dyad are considered. The binding of fullerenes to M-pro is due to shape complementarity, i.e., vdW interactions, and is aspecific. As such, it is not sensitive to mutations that can eliminate or invert the charges of the amino acids composing the binding pocket. Fullerenic cages should therefore be more effective against the SARS-CoV-2 virus than the available inhibitors such as masinitib, where the electrostatic term plays a crucial role in the binding

The stability and dispersion of carbon nanotube-polymer solutions: A molecular dynamics study

Carbon nanotubes have been explored to increase the mechanical properties and electrical conductivity of polymeric fibers through compounding with polymer to be extruded into fibers. However, this route creates major challenges because carbon nanotubes have strong cohesion and tend to aggregate and precipitate due to their poor interfacial interaction with polymers. In this study, classical molecular dynamics simulations are used to predict and characterize carbon nanotubes-polymer interface mechanism in two different polymer matrices: polyvinyl butyral and polystyrene-co-glycidyl methacrylate. The dominated interface mechanisms are discovered to shed light on carbon nanotubes dispersion in solvent based systems and to explore the prerequisites for stabilized nanofluids. Our results showed that π-stacking interactions between aromatic groups and graphene surfaces of carbon nanotubes as in polystyrene-co-glycidyl methacrylate systems, play an important role in dispersion of carbon nanotubes, whereas slight repulsions between carbon nanotubes and polyvinyl butyral chains lead to large morphological differences and carbon nanotubes bundles in many chain systems. Altogether, the results indicated that polymers with structures having strong interactions with the surfaces of carbon nanotubes through π–π interactions are more effective in dispersing carbon nanotubes and caused stabilized solutions in wet fiber processing

Engineering the Fullerene-protein Interface by Computational Design: The Sum is More than its Parts

Of all the amino acids, the surface of \u3c0-electron conjugated carbon nanoparticles has the largest affinity for tryptophan, followed by tyrosine, phenylalanine, and histidine. In order to increase the binding of a protein to a fullerene, it should suffice to mutate a residue of the site that binds to the fullerene to tryptophan, Trp. Computational chemistry shows that this intuitive approach is fraught with danger. Mutation of a binding residue to Trp may even destabilize the binding because of the complicated balance between van der Waals, polar and non-polar solvation interactions

Biocompatible and Light-Penetrating Hydrogels for Water Decontamination

Solar light-activated photocatalyst nanoparticles (NPs) are promising environment-friendly low cost tools for water decontamination, but their dispersion in the environment must be minimized. Here, we propose the incorporation of TiO2-NPs (also in combination with graphene platelets) into highly biocompatible hydrogels as a promising approach for the production of photoactive materials for water treatment. We also propose a convenient fluorescence-based method to investigate the hydrogel photocatalytic activity in real time with a conventional fluorimeter. Kinetics analysis of the degradation profile of a target fluorescent model pollutant demonstrates that fast degradation occurs in the matrix bulk. Fluorescence anisotropy proved that small pollutant molecules diffuse freely in the hydrogel. Rheological and scanning electron microscopy characterization showed that the TiO2-NP incorporation does not significantly alter the hydrogel mechanical and morphological properties

Dissecting the supramolecular dispersion of fullerenes by proteins/peptides: Amino acid ranking and driving forces for binding to c60

Molecular dynamics simulations were used to quantitatively investigate the interactions between the twenty proteinogenic amino acids and C60. The conserved amino acid backbone gave a constant energetic interaction ~5.4 kcal mol−1, while the contribution to the binding due to the amino acid side chains was found to be up to ~5 kcal mol−1 for tryptophan but lower, to a point where it was slightly destabilizing, for glutamic acid. The effects of the interplay between van der Waals, hydrophobic, and polar solvation interactions on the various aspects of the binding of the amino acids, which were grouped as aromatic, charged, polar and hydrophobic, are discussed. Although π–π interactions were dominant, surfactant‐like and hydrophobic effects were also observed. In the molecular dynamics simulations, the interacting residues displayed a tendency to visit configura-tions (i.e., regions of the Ramachandran plot) that were absent when C60 was not present. The amino acid backbone assumed a “tepee‐like” geometrical structure to maximize interactions with the fullerene cage. Well‐defined conformations of the most interactive amino acids (Trp, Arg, Met) side chains were identified upon C60 binding