Lactoferrin adsorption onto silver nanoparticle interface: Implications of corona on protein conformation, nanoparticle cytotoxicity and the formulation adjuvanticity

Abstract

Nanoparticle, in biological milieu, tends to bind a variety of biomolecules, especially protein, forming an interfacial corona that provides biological identity to nanoparticle. Understanding the protein corona is likely to provide insight in nanoparticle bio-distribution, nanoparticle-mediated cytotoxicity and potential nanoparticle-mediated applications. Thus, the bovine lactoferrin (BLf) corona onto silver nanoparticle (AgNP) interface is studied with reference to BLf conformational stability and the resulting complex’s cytotoxic and adjuvant properties. The adsorption of BLf onto AgNP interface is reflected by change in the particle-specific surface plasmon resonance (SPR). Additionally, the molecular dynamics (MD) simulation deciphered the binding energy and molecular recognition in BLf and AgNP complex. Protein adsorption onto the interface is majorly driven by van der Waals interactions and hydrogen bonds, without any significant effect on the protein conformation and stability. BLf retains bacteriostatic property in the conjugate, and the presence of BLf corona ameliorated the particle-mediated cytotoxicity, despite the enhanced cellular internalization. Additionally, BLf adsorbed AgNP formulation shows better adjuvanticity than AgNP only or BLf only formulation, as demonstrated using Bacillus anthracis protective antigen protein, in vivo.