POLYMER COMPOSITION AND FUNCTIONAL EFFECTS OF THE SPECIES-SPECIFIC BIOMOLECULAR CORONA FORMATION ON NPs

This dissertation describes how by modulating the structural parameters of polymer brushes, specifically, dispersity within brushes can play an important role in regulating their physicochemical properties, thus presenting a significant approach for the design of future technologically relevant biomaterials. In Chapter 1, I provide a brief introduction about the application of polymer brushes to nanoparticles (NPs) to regulate their interactions with proteins in physiological environments, along with recent advances in this field. First, the key parameters that determine the formation and composition of a protein corona (PC) and the response of the immune system to circulating NPs are presented. Then, the effect of dense brush coatings used to protect NPs from non-specific protein adsorption and cellular uptake are deeply described. Finally, an overview of polyethylene glycol (PEG) and alternative polymers used to generate those brush shells on NPs and the correlation between structural parameters like topology or dispersity and biopassivity are highlighted. In Chapter 2, I describe the control of dispersity within brushes of poly[(oligoethylene glycol)methacrylate]s (POEGMAs) on flat surfaces and its effect to their physicochemical properties. POEGMAs, due to their bioinertness and facile synthesis, have raised as a promising alternative to poly(ethylene glycols) (PEGs) in a wide range of biomedical applications, especially when they are applied as polymer brush coatings. Commercially available OEG-methacrylate macromonomers feature a broad distribution of OEG lengths generating structurally polydisperse POEGMAs. Here, interfacial physicochemical properties of POEGMA brushes are significantly affected by their structural dispersity (i.e., degree of heterogeneity in the length of side OEG segments). In contrast to previous assumptions, the properties of POEGMA brushes cannot be accurately predicted without considering the impact of dispersity in the (macro)monomer feeds. In Chapter 3, I report the effect of dispersity within brushes of POEGMA brushes on spherical surfaces, specifically, gold nanoparticles (AuNPs), on their colloidal stability, protein adsorption, and antibody recognition. By simply adjusting the degree of heterogeneity in the OEG lengths, NPs in physiological media can achieve better disaggregation and enhanced colloidal stability when subjected to a temperature ramp. This effect is particularly pronounced in those NPs with a more homogeneous structure grafted. Moreover, after generating a PC on the NPs, several techniques (e.g., SDS-PAGE with silver or Coomassie staining and Bradford test) indicate no significant differences in the protein composition and quantification, hence, revealing that the antifouling properties remain intact. However, when a self-assemble monolayer (SAM) is generated on a surface plasmon resonance (SPR) chip of POEGMA brushes and anti-PEG antibodies (APAs) are circulating at different concentrations, more binding is detected on the more heterogenous side-chain OEG lengths.