Nanoparticle-Protein Interaction: Demystifying the Correlation between Protein Corona and Aggregation Phenomena.

Protein corona formation and nanoparticles' aggregation have been heavily discussed over the past years since the lack of fine-mapping of these two combined effects has hindered the targeted delivery evolution and the personalized nanomedicine development. We present a multitechnique approach that combines dynamic light and small-angle X-ray scattering techniques with cryotransmission electron microscopy in a given fashion that efficiently distinguishes protein corona from aggregates formation. This methodology was tested using ∼25 nm model silica nanoparticles incubated with either model proteins or biologically relevant proteomes (such as fetal bovine serum and human plasma) in low and high ionic strength buffers to precisely tune particle-to-protein interactions. In this work, we were able to differentiate protein corona, small aggregates formation, and massive aggregation, as well as obtain fractal information on the aggregates reliably and straightforwardly. The strategy presented here can be expanded to other particle-to-protein mixtures and might be employed as a quality control platform for samples that undergo biological tests.

A nano perspective behind the COVID-19 pandemic.

The global pandemic scenario has definitely pushed the scientific community to develop COVID-19 vaccines at unprecedented speed. Nevertheless, a worldwide vaccination campaign is still far from being achieved, making the usual precautionary measures as necessary as at the beginning of the outbreak. Many aspects of the SARS-CoV-2 infectious potential and disease severity do not solely rely on interactions at the molecular level but also on physical-chemical parameters that often involve nanoscale effects. Here the SARS-CoV-2 journey to infect a susceptible host is reviewed, focusing on the nanoscale aspects that play a role in the viral infectivity and disease progression. These nanoscale-driven interactions are essential to establish mitigation-related strategies.

Colloidal Stability and Redispersibility of Mesoporous Silica Nanoparticles in Biological Media.

The outreach of nanoparticle-based medical treatments has been severely hampered due to the imbalance between the efforts in designing extremely complex materials and the general lack of studies devoted to understanding their colloidal stability in biological environments. Over the years, the scientific community has neglected the relevance related to the nanoparticles' colloidal state, which consequently resulted in very poor bench-to-clinic translation. In this work, we show how mesoporous silica nanoparticles (MSNs, one of the most promising and tested drug delivery platforms) can be efficiently synthesized and prepared, resulting in a colloidally stable system. We first compared three distinct methods of template removal of MSNs and evaluated their ultimate colloidal stability. Then, we also proposed a simple way to prevent aggregation during the drying step by adsorbing BSA onto MSNs. The surface modification resulted in colloidally stable particles that are successfully redispersed in biologically relevant medium while retaining high hemocompatibility and low cytotoxicity.

Effect of particle functionalization and solution properties on the adsorption of bovine serum albumin and lysozyme onto silica nanoparticles.

Silica nanoparticles present an enormous potential as controlled drug delivery systems with high selectivity towards diseased cells. This application is directly related to the phenomenon of protein corona, characterized by the spontaneous adsorption of proteins on the nanoparticle surface, which is not fully understood. Here, we report an investigation on the influence of pH, ionic strength and temperature on the thermodynamics of interaction of bovine serum albumin protein (BSA) with non-functionalized silica nanoparticles (SiO2NPs). Complementary, we also investigated the ability of polyethylene glycol (PEG) and zwitterionic sulfobetaine (SBS) surface-modified nanoparticles to prevent the adsorption of BSA (protein negatively charged at physiological pH) and lysozyme (protein positively charged at physiological pH). We showed that BSA interaction with SiO2NPs is enthalpically governed. On the other hand, functionalization of silica nanoparticles with PEG and SBS completely prevented BSA adsorption. However, these functionalized nanoparticles presented a negative zeta potential and were not able to suppress lysozyme anchoring due to strong nanoparticle-protein electrostatic attraction. Due to the similarity of BSA with Human Serum Albumin, this investigation bears a resemblance to processes involved in the phenomenon of protein corona in human blood, producing information that is relevant for the future biomedical use of functionalized nanoparticles.

The influence of ZnII coordination sphere and chemical structure over the reactivity of metallo-ß-lactamase model compounds.

A systematic study of the influence of the first coordination sphere over the reactivity and structure of metallo-ß-lactamase (MßL) monozinc model complexes is reported. Three ZnII complexes with tripodal ligands forming the series [Zn(N-NNN)], [Zn(N-NNS)], and [Zn(N-NNO)] where N-NNX represents the tripodal donor atoms were investigated regarding their ability to mimic MßL. The tripodal series was inspired by MßL active sites in the respective subclasses, representing the (His, His, His) Zn1 site present in B1 and B3 subclasses, (His, His, Asp) present in the B3 subclass site and the thiolate present in B1 and B2 sites. The results were supported by electronic structure calculations. XAS analysis demonstrated that the ZnII electronic deficiency significantly changes in the order [Zn(N-NNS)] < [Zn(N-NNN)] < [Zn(N-NNO)]. This effect directly affects the reactivity over nitrocefin and amoxicillin, observed by the hydrolysis kinetics, which follows the same trend. NMR spectroscopy revealed the coordination of the carboxylic group in the substrate to the metal changes accordingly, affecting the hydrolysis kinetics. Our results also demonstrated that not only the Lewis acidity is changed by the ligand system but also the softness of the metal. [Zn(N-NNS)] is softened by the thiolate, promoting the ligand substitution reaction with solvents and favoring a secondary interaction with substrates, not observed for [Zn(N-NNO)]. XRD of the models reveals their similar geometric aspects in comparison to the crystal structure of GOB MßL. The present work demonstrates that the ZnII electronic details must be considered in the design of new MßL models that will further aid in the design of clinically useful inhibitors.