After a short background discussing engineered nanomaterials (ENMs) and their physicochemical properties and applications, the present perspective paper highlights the main specific points that need to be considered when examining the question of neurotoxicity of nanomaterials. It underlines the necessity to integrate parameters, specific tools, and tests from multiple sources that make neurotoxicology when applied to nanomaterials particularly complex. Bringing together the knowledge of multiple disciplines e.g., nanotoxicology to neurotoxicology, is necessary to build integrated neurotoxicology for the third decade of the 21st Century. This article focuses on the greatest challenges and opportunities offered by this specific field. It highlights the scientific, methodological, political, regulatory, and educational issues. Scientific and methodological challenges include the determination of ENMs physicochemical parameters, the lack of information about protein corona modes of action, target organs, and cells and dose- response functions of ENMs. The need of standardization of data collection and harmonization of dedicated neurotoxicological protocols are also addressed. This article highlights how to address those challenges through innovative methods and tools, and our work also ventures to sketch the first list of substances that should be urgently prioritized for human modern neurotoxicology. Finally, political support with dedicated funding at the national and international levels must also be used to engage the communities concerned to set up dedicated educational program on this novel field.

The protein adsorption onto poly(acrylic acid)-block-polystyrene (PAA22-b-PS144) polymersomes has been investigated with regard to structural features, thermodynamic aspects and biological consequences. The light scattering measurements revealed the formation of protein coronas enveloping the polymeric capsules regardless of the chemical nature of the biomacromolecules. The experiments were conducted by using lysozyme, immunoglobulin G - IgG and bovine serum albumin - BSA as model proteins due to their differences concerning size and residual surface charge at physiological pH. The protein adsorption was further confirmed by isothermal titration calorimetry, and the experimental data suggest that the phenomenon is mainly governed by hydrogen bonding and van der Waals interactions. The pre-existing protein layer via the pre-incubation in protein environments notably attenuates the cytotoxicity of the nanomaterial compared to the pristine counterparts. This approach can possibly be extended to different types of assemblies when intermolecular interactions are able to induce protein adsorption and the development of protein coronas around nanoparticles. Such fairly simple method may be convenient to engineer safer nanomaterials towards a variety of biomedical applications when the nanotoxicity is an issue. Additionally, the strategy can possibly be used to tailor the surface properties of nanoparticles by adsorbing specific proteins for targeting purposes.

Carbon nanotubes (CNTs) are one of the unique and promising nanomaterials that possess plenty of applications, such as biosensors, advanced drug delivery systems and biotechnology. CNTs bind rapidly with proteins, which result in the formation of a protein coating layer known as a \"protein corona\" around the surface of the nanomaterial. This hinders their applications as a drug carrier and influences the properties of biological macromolecules. The present work focuses on studying the thermal stability and molecular level interactions of two heme proteins, hemoglobin (Hb) and myoglobin (Mb), in the presence of carboxylated functionalized multi-walled CNTs (CA-MWCNTs). Through the current study, the following steps have been taken to distinguish the biocompatibility of the hydrophilic surface CA-MWCNTs for heme proteins via a series of spectroscopic techniques and differential scanning calorimetry (DSC). UV-Visible and steady-state fluorescence spectroscopy were used to reveal changes in the aromatic amino acid residues of heme proteins upon the addition of CA-MWCNTs. Circular dichroism spectroscopy (CD) shows the alteration in the native structure of proteins in the presence of the nanomaterial. A tremendous increase in the size of the protein CA-MWCNTs system is observed in dynamic light scattering (DLS), which clearly manifests the protein corona formation. Unexpectedly, both proteins interact differently with CA-MWCNTs, which is observed in CD spectroscopy and DSC. In the presence of CA-MWCNTs, an increase in the transition temperature (Tm) was observed for Hb, while the Tm value decreases for Mb. Different interactions with proteins at the molecular scale may be the reason for this unexpected behavior. Henceforth, the present results can help in the design of the next-generation drug carrier nanomaterials with the idea of the heme protein corona formation prior to development.