Non-equilibrium transport of nanoparticles across the lipid membrane

Development of effective strategies for the internalization of nanoparticles is essential in many applications, such as drug delivery. Most, if not all, previous studies are based on equilibrium considerations. In this work, inspired by the recent development of a pro-drug delivery strategy based on reversible esterification, we consider a non-equilibrium transport mechanism for nanoparticles of a 6 nm diameter across the lipid membrane. We divide the transport process into insertion and ejection steps, which are studied with coarse-grained models using free energy and reactive Monte Carlo simulations, respectively. The simulations show that the non-equilibrium transport efficiency is relatively insensitive to the fraction of reactive surface ligands once a modest threshold is surpassed, while the distribution pattern of different (hydrophilic, reactive and permanent hydrophobic) ligands on the nanoparticle surface has a notable impact on both the insertion and ejection steps. Our study thus supports a novel avenue for designing nanoparticles that are able to be efficiently internalized and provides a set of relevant guidelines for surface functionalization.

Automated summary

In this study, a non-equilibrium transport mechanism for 6 nm diameter nanoparticles across lipid membranes is investigated. The simulations show that the transport efficiency is relatively insensitive to the fraction of reactive surface ligands, but the distribution pattern of different ligands on the nanoparticle surface has a notable impact on both insertion and ejection steps. This study provides a novel approach for designing efficient internalization of nanoparticles and offers guidelines for surface functionalization.