Recent Advances in Immunosafety and Nanoinformatics of Two-Dimensional Materials Applied to Nano-imaging.

Two-dimensional (2D) materials have emerged as an important class of nanomaterials for technological innovation due to their remarkable physicochemical properties, including sheet-like morphology and minimal thickness, high surface area, tuneable chemical composition, and surface functionalization. These materials are being proposed for new applications in energy, health, and the environment; these are all strategic society sectors toward sustainable development. Specifically, 2D materials for nano-imaging have shown exciting opportunities in in vitro and in vivo models, providing novel molecular imaging techniques such as computed tomography, magnetic resonance imaging, fluorescence and luminescence optical imaging and others. Therefore, given the growing interest in 2D materials, it is mandatory to evaluate their impact on the immune system in a broader sense, because it is responsible for detecting and eliminating foreign agents in living organisms. This mini-review presents an overview on the frontier of research involving 2D materials applications, nano-imaging and their immunosafety aspects. Finally, we highlight the importance of nanoinformatics approaches and computational modeling for a deeper understanding of the links between nanomaterial physicochemical properties and biological responses (immunotoxicity/biocompatibility) towards enabling immunosafety-by-design 2D materials.

Understanding the driving forces of camptothecin interactions on the surface of nanocomposites based on graphene oxide decorated with silica nanoparticles.

Camptothecin (CPT) is a potent antitumor drug frequently used in studies of drug delivery systems. The poor water solubility and unfavourable pharmacokinetic conditions of CPT and the development of nanomaterials such as mesoporous silica nanoparticles (MSNs), graphene oxide (GO) and a new family of GO decorated with MSNs (GO-MSNs) motivated the present work, which sought to solve these challenges. In this context, release assays showed rapid and prolonged release, respectively, by silica and GO/GO-MSN nanomaterials; release was faster at pH 7.4 and slower at pH 5.0 in all situations. In particular, GO-MSNs presented an important advantage compared to GO due to their slower drug release at pH 7.4 (physiological conditions in blood; slowest release is expected under these conditions) and faster drug delivery at pH 5.0 (acidic conditions in endosomes of cancer cells; fastest release is expected under these conditions). The results, therefore, present the GO-MSN nanomaterial as a potential candidate for antitumor applications. The main drug-nanocarrier chemical interactions (London forces, hydrogen bonds, and electrostatic and dipole-dipole interactions) are also exhaustively described in order to understand the observed differences in drug delivery properties among these nanomaterials and to comprehend the influence of pH on concomitant and dynamic interactions.

Biological effects of oxidized carbon nanomaterials (1D versus 2D) on Spodoptera frugiperda: Material dimensionality influences on the insect development, performance and nutritional physiology.

In this work, we developed an integrative experimental design to investigate the long-term effects of two important classes of carbon nanomaterials with different dimensionalities (i.e., 1D oxidized multiwalled carbon nanotube, ox-MWCNT, and 2D graphene oxide, GO) on the development of the generalist insect Spodoptera frugiperda (Lepidoptera: Noctuidae). Insects are exciting in vivo biological models for investigating the impact of nanomaterials on nanobio-ecological interactions. S. frugiperda larvae were reared from egg hatching to pupation on diets containing ox-MWCNT and GO at different concentrations (0, 10, 100 and 1000 µg g-1 of dry mass of diet). Several aspects of larval and adult performance were measured under controlled conditions. The effects of the carbon nanomaterial (CNM)-containing diets on the nutritional physiology and digestive enzymatic activities of S. frugiperda larvae were also evaluated. The results showed that the type and concentration of CNMs in the diet negatively affected the reproductive parameters and the digestive and metabolic efficiency of S. frugiperda. The diet containing the highest concentration of GO significantly reduced the fecundity and fertility of S. frugiperda compared to the effects of other treatments. S. frugiperda larvae showed decreased efficiency of food conversion into biomass and maximal approximate digestibility when fed diets containing GO at higher concentrations. However, quantitative differences in digestive enzyme activities were not observed between all treatments. These findings highlighted the critical influence of CNM dimensionality on the general performance and nutritional physiology of the moth. This work contributes to the safety evaluation and future applications of CNMs in agri-environmental nanotechnology.

Covalent functionalization of graphene oxide with d-mannose: evaluating the hemolytic effect and protein corona formation.

In this work, graphene oxide (GO) was covalently functionalized with d-mannose (man-GO) using mannosylated ethylenediamine. XPS (C1s and N1s) confirmed the functionalization of GO through the binding energies at 288.2 eV and 399.8 eV, respectively, which are attributed to the amide bond. ATR-FTIR spectroscopy showed an increase in the amine bond intensity, at 1625 cm-1 (stretching C[double bond, length as m-dash]O), after the functionalization step. Furthermore, the man-GO toxicity to human red blood cells (hemolysis) and its nanobiointeractions with human plasma proteins (hard corona formation) were evaluated. The mannosylation of GO drastically reduced its toxicity to red blood cells. SDS-PAGE analysis showed that the mannosylation process of GO also drastically reduced the amount of the proteins in the hard corona. Additionally, proteomics analysis by LC-MS/MS revealed 109 proteins in the composition of the man-GO hard corona. Finally, this work contributes to future biomedical applications of graphene-based materials functionalized with active biomolecules.

Microwave-assisted synthesis of palladium nanoparticles intercalated nitrogen doped reduced graphene oxide and their electrocatalytic activity for direct-ethanol fuel cells.

Palladium nanoparticles decorated reduced graphene oxide (Pd-rGO) and palladium nanoparticles intercalated inside nitrogen doped reduced graphene oxide (Pd-NrGO) hybrids have been synthesized by applying a very simple, fast and economic route using microwave-assisted in-situ reduction and exfoliation method. The Pd-NrGO hybrids materials show good activity as catalyst for ethanol electro oxidation for direct ethanol fuel cells (DEFCs) as compared to Pd-rGO hybrids. The enhanced direct ethanol fuel cell can serve as alternative to fossil fuels because it is renewable and environmentally-friendly with a high energy conversion efficiency and low pollutant emission. As proof of concept, the electrocatalytic activity of Pd-NrGO hybrid material was accessed by cyclic voltammetry in presence of ethanol to evaluate its applicability in direct-ethanol fuel cells (DEFCs). The Pd-NrGO catalyst presented higher electro active surface area (∼6.3 m2 g-1) for ethanol electro-oxidation when compared to Pd-rGO hybrids (∼3.7 m2 g-1). Despite the smaller catalytic activity of Pd-NrGO, which was attributed to the lower exfoliation rate of this material in relation to the Pd-rGO, Pd-NrGO showed to be very promising and its catalytic activity can be further improved by tuning the synthesis parameters to increase the exfoliation rate.

Topography-driven bionano-interactions on colloidal silica nanoparticles.

We report here that the surface topography of colloidal mesoporous silica nanoparticles (MSNs) plays a key role on their bionano-interactions by driving the adsorption of biomolecules on the nanoparticle through a matching mechanism between the surface cavities characteristics and the biomolecules stereochemistry. This conclusion was drawn by analyzing the biophysicochemical properties of colloidal MSNs in the presence of single biomolecules, such as alginate or bovine serum albumin (BSA), as well as dispersed in a complex biofluid, such as human blood plasma. When dispersed in phosphate buffered saline media containing alginate or BSA, monodisperse spherical MSNs interact with linear biopolymers such as alginate and with a globular protein such as bovine serum albumin (BSA) independently of the surface charge sign (i.e. positive or negative), thus leading to a decrease in the surface energy and to the colloidal stabilization of these nanoparticles. In contrast, silica nanoparticles with irregular surface topographies are not colloidally stabilized in the presence of alginate but they are electrosterically stabilized by BSA through a sorption mechanism that implies reversible conformation changes of the protein, as evidenced by circular dichroism (CD). The match between the biomolecule size and stereochemistry with the nanoparticle surface cavities characteristics reflects on the nanoparticle surface area that is accessible for each biomolecule to interact and stabilize any non-rigid nanoparticles. On the other hand, in contact with variety of biomolecules such as those present in blood plasma (55%), MSNs are colloidally stabilized regardless of the topography and surface charge, although the identity of the protein corona responsible for this stabilization is influenced by the surface topography and surface charge. Therefore, the biofluid in which nanoparticles are introduced plays an important role on their physicochemical behavior synergistically with their inherent characteristics (e.g., surface topography).