Role of Ligand Conformation on Nanoparticle-Protein Interactions

TL;DR

This study uses computational methods to explore how ligand conformation and surface chemistry of gold nanoparticles influence their interaction with serum proteins, impacting nanoparticle design for biomedical applications.

Contribution

It reveals how ligand chemical composition and conformational preferences affect nanoparticle-protein interactions, informing design of corona-free nanoparticles.

Findings

Ligand charge and hydrophobicity influence HSA binding.

Ligand conformational preferences modulate nanoparticle-protein interactions.

Surface chemistry determines the likelihood of protein corona formation.

Abstract

Engineered biomedical nanoparticles (NP) administered via intravenous routes are prone to associate to serum proteins. The protein corona can mask the NP surface functionalization and hamper the delivery of the NP to its biological target. The design of corona-free NPs relies on our understanding of the chemical-physical features of the NP surface driving the interaction with serum proteins. Here we address, by computational means, the interaction between human serum albumin (HSA) and a prototypical monolayer-protected Au nanoparticle. We show that both the chemical composition (charge, hydrophobicity) and the conformational preferences of the ligands decorating the NP surface affect the NP propensity to bind HSA.