Engineering nanomaterial surfaces for biomedical applications: antiviral surface coatings, antiviral nanoparticles and lipid-based biopharmaceutical drug systems

Nanomaterial surfaces can be engineered by chemical modifications for the modulation of various surface properties including surface charges, hydrophobicity and chemical reactivity. These properties modulate in turn the interactions between the nanomaterials and biological systems, subsequently enabling some material functions, including viral inactivation and cell membrane penetration. In this thesis, we engineer nanomaterial surfaces to address the challenges in antiviral surface coatings, antiviral nanoparticles and biopharmaceutical drug delivery carriers.

Conventional antiviral surface coatings are either made of fossil fuel-derived polymers or of metals, both have the sustainability and durability challenge. We show that antiviral surfaces can be made with phenol-rich soda lignin to address the sustainability challenge. We also show that antiviral surfaces can be engineered with anionic polymers supramolecularly loaded with antiviral compounds including quaternary ammonium compounds and copper salts, so to address the durability challenge. Virucidal multivalent nanoparticles have been demonstrated promising as broad-spectrum antiviral therapeutics. However, how the ligand density and the nanoparticle curvature affect the antiviral activity was not known. We have engineered silica nanoparticles with various ligand densities and nanoparticle core sizes, and shown that the viral inhibition is determined by equivalent solution concentration of the antiviral ligands. We also show that silica nanoparticles with a diameter in the range of 4 to 200 nm are all virucidal. These results enable a broader NP selection for engineering virucidal multivalent nanoparticles.

Lipid-based nanocarriers are challenging for cytosolic delivery of therapeutic proteins due to the complexity of their surface properties. We show that this challenge can be addressed by modifying the surface of proteins with cationic lipids. The surface engineering enables the direct cytosol penetration of differently charged proteins, without compromising cell membrane integrity. This overcomes the cytotoxicity challenge of cationic nanocarriers.

Large lipid nanoparticles (100 to 200 nm in diameter) are preferred delivery carriers for mRNA vaccines due to the augmented immune stimulation effects. However, synthesizing large lipid nanoparticles while maintaining low polydispersity index (< 0.1) remains a major challenge. We engineer lipid nanoparticles surfaces with PEG-lipids and fluorescent lipids, and show that depletion force induces lipid nanoparticle fusion, subsequently enabling the synthesis of large LNPs with low polydispersity index.