Bio-nano interactions of metal-phenolic networks: the role of metals

Abstract

Metal-phenolic networks (MPNs) hold great promise for the fabrication of multifunctional hybrid materials owing to their versatile and tunable nature. In particular, the beneficial combination of both organic and inorganic components makes them highly interesting systems for a range of applications. Because of the ease of changing the metal ions and ligands, they are highly interesting materials for drug delivery, cell targeting, medical imaging, and catalysis. Metal ions are known to bind to a variety of biomolecules, for example amyloid beta peptides and antibodies. However, to date, the bio-nano interactions of MPNs are not fully understood, especially for the role of metals. In this PhD research, bio-nano interactions of MPN- coated gold nanoparticles (AuNP@MPNs) with different biomolecules were studied to reveal the role of metals.

In the first part of this PhD research, the potential of AuNP@MPNs for amyloid fibril inhibition was investigated. Metal ions and polyphenols have been demonstrated to separately play an important role in the amyloid fibril progression and in the inhibition of fibril formation, respectively, and therefore in combination should have synergistic effects. Numerous diseases, such as Alzheimer’s disease and Type II Diabetes, are potentially associated with the formation of amyloid fibrils. In this systematic study, metal ions were varied in the MPN system, with Co-TA (cobalt-tannic acid)-coated AuNPs showing the highest inhibition ability. Molecular dynamics simulations and quantum mechanics calculations suggested that the geometry of the exposed cobalt coordination site in the cobalt-tannic acid networks facilitated its favorable interactions with histidine and methionine residues in the amyloid beta peptides. Like amyloid fibrils, antibodies can interact with transition metals (e.g., CoII, NiII, CuII, ZnII) via the histidine-rich domain at Fc region in an oriented manner. In the second part of this PhD research, AuNP@MPNs were modified with antibodies by adsorption and their targeting abilities were studied. Similar antibody loading levels were observed for all AuNP@MPNs with different metals. However, the Co-TA coated AuNPs adsorbed with antibodies again showed a different behavior compared to the other metals. It possessed improved targeting towards both antigens and cells by inducing the potential orientation (conformation) change of the adsorbed antibodies, which further confirmed the unique property of cobalt in the bio-nano interactions of MPNs. The third part of this PhD research further investigated the bio-nano interactions of AuNP@MPNs in the complex protein system – human serum. As tannic acid might dominate the bio-nano interactions, the effects of different ligands were examined along with the effects of the different metals. It was found that the protein corona can reduce the cell association of all AuNPs investigated. The amount and composition of corona proteins were evaluated by both SDS-PAGE and LC-MS/MS. MPNs with tannic acid as the phenolic ligand showed no significant difference with varied metals in both corona protein content and cell association. However, MPNs with gallic acid as the ligand showed that FeIII and ZnII exhibited different corona protein content and cell association compared to other metals. These findings suggested that bulky tannic acid may dominate the adsorption of biomolecules while cobalt can contribute to the conformation of biomolecules by coordination. Taken together, this research provides a fundamental understanding of MPNs for future bio-nano related applications.