Amphiphilic Nanostructures from Block and Gradient Poly(2-oxazoline) Copolymers: Understanding Protein Corona Formation and its Relation to Nanoparticle Structural Features

• Grant number: 24/09935-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: March 01, 2025
• End date: February 29, 2028
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Physical-Chemistry
• Principal Investigator: Fernando Carlos Giacomelli
• Grantee: Fernando Augusto de Oliveira
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
• Associated research grant: 21/12071-6 - Tailoring colloids through supramolecular interactions: from fundamentals to applications, AP.TEM

Abstract

The protein corona formation in biological fluids challenges our understanding and exploitation of nanomaterials designed for sensing and nanomedicine. Over the past years, active research gas been focused on elucidating the driving forces on protein corona formation as well as its biological benefits and drawbacks. The consequences of bio-nano interactions are multifold as they may mask the chemical and biological functionalities imparted to the nanoparticle in the laboratory nevertheless, they can also reduce the toxicity of the produced nanomaterials, for instance. In this framework, this proposal regards to a comprehensive investigation on polymer colloids at biological environments involving self-assembly, behavior in protein milieus and interaction with living systems. The investigations will start from the macromolecular self-assembly of block and gradient copolymers having hydrophilic 2-methyl-2-oxazoline and hydrophobic 2-phenyl-2-oxazoline as repeating units. The choice of PMeOx/PEtOx over the more commonly used polyethylene glycol (PEG) is driven by increasing concerns regarding PEG, such as the occurrence of anti-PEG antibodies in the human population, which can cause accelerated clearance and potential allergic reactions upon administration of PEGylated therapeutics and vaccines. Nevertheless, protein adsorption on poly(2-oxazoline)-based (PAOx) nanoparticles has been far less explored compared to PEG-coated counterparts. Additionally, block vs. gradient PAOx supramolecular structures have different self-assembled and internal structures, but the effect on protein interactions of micelles based on copolymers with different monomer distributions is unknown. The assemblies will be firstly characterized by using scattering techniques and cryo transmission electron microscopy to properly understand their structural features. Subsequently, the adsorption of model proteins (HSA - human serum albumin, fibrinogen, IgG - Immunoglobulin G, APoE - apolipoprotein E and lysozyme) onto the surface of the produced polymeric assemblies will be evaluated to gain fundamental understanding on the relation of their structural features (morphology, size, shape, chemical nature, surface charge, surface curvature, chain length, chain density, hydrophobicity) on protein binding. The main objective of this proposal is to fundamentally understand the nanobiointerface between polymeric carriers and biological media comprehending how the structural characteristics of the nanomaterials influence protein adsorption behavior quantitively and qualitatively. Lastly, we will probe how protein adsorption influences important biological outputs namely: cellular uptake behavior and intracellular trafficking.