Silica nanoparticles degradation in physiologic media: morphology, colloidal stability and surface interactions evolution

Abstract

Recent advances in nanomedicine aim to develop safe nanomaterials with high biological performance and drug load, distribution, and delivery capabilities. In this context, nanoparticles (NPs) with biodegradable properties can avoid unwanted scenarios, such as bioaccumulation, and be safely cleared by the immune system after degradation. Still, little is understood about the evolution of NPs in the degradation process, which entails a need to investigate these complex systems deeply. Thus, this study aims to monitor the evolution of NP's under degrading conditions, observing the morphology, colloidal stability, and protein adsorption, the latter being one of the main limiting factors in implementing nanocarriers. Three model systems will be considered, the degradable silica nanoparticle (SiO2NP-D) without functionalization, SiO2NP-D functionalized with zwitterionic groups, and SiO2NP-D functionalized with polyethylene glycol (PEG). Silica nanoparticles are promising model platforms, and their functionalization makes the undesirable adsorption of proteins (a phenomenon known as protein corona) unlikely to occur. The monitoring of SiO2NP aspects in degrading conditions will be based on the combination of characterization techniques, such as small angle X-ray scattering (SAXS) and transmission cryo-microscopy (Crio-TEM) techniques, recently reported by the research group and proved to be innovative in the study of model systems. Here, the aim is to advance this characterization methodology, together with adjuvant techniques (synchrotron radiation circular dichroism - SRCD, dynamic light scattering - DLS, and isothermal titration calorimetry - ITC) in the description of complex systems. The proposal presented here aims to mimic the processes of biodegradation and clearance of nanocarriers in human physiological fluids, which brings relevance to this study to produce results that will contribute to advances in nanomedicine. (AU)