Computational Studies of Lipid-Wrapped Gold Nanoparticle Transport Through Model Lung Surfactant Monolayers

Abstract

Colloidal nanoparticles, such as gold nanoparticles (AuNPs), are promising materials for the delivery of hydrophilic drugs via the pulmonary route. The inhaled nanoparticle drug carriers primarily deposit in lung alveoli and interact with the alveolar surface known as lung surfactants. Therefore, it is vital to understand the interactions of nanocarriers with the surfactant layer. To understand the interactions at the molecular level, here we simulated model lung surfactant monolayers with phospholipid (PL)-wrapped AuNPs at the vacuum–water interface using coarse-grained molecular dynamics simulations. The PL-wrapped AuNPs quickly adsorbed into the surfactant layer, altered the structural properties of the monolayer, and at high concentrations initiated the compressed monolayer to collapse/buckle. Among the surfactant monolayer lipid components, cholesterol adsorbed to the AuNPs preferentially over PL species. The position of the adsorbed PL-AuNPs within the monolayer, and subsequent monolayer perturbation, vary depending on the monolayer phase, monolayer composition, and species of PL used as a ligand. Information provided by these molecular dynamic simulations helps to rationalize why some colloidal nanoparticles work better as nanocarriers than others and aid the design of new ones, to avoid biological toxicity and improve efficacy for pulmonary drug delivery.

Shape matters—the interaction of gold nanoparticles with model lung surfactant monolayers

“…As a result, the monolayer has a higher APL of 0.538 ± 0.001 nm 2 in simulations with a surface tension of 23 mN m −1 . These values are in excellent agreement with previous simulation studies of LSMs with comparable composition [37,60].…”

Molecular basis of transport of surface functionalised gold nanoparticles to pulmonary surfactant

“…31 MD simulations are an effective way to research the translocation of NPs into monolayer at a molecular level that is otherwise not available using experimental biophysical characterisation techniques. Coarse-grained molecular dynamics (CGMD) simulations have been used to research the structural changes in PS due to the inhalation of different NPs like carbon fullerene, nanotubes, graphene, silica, calcium sulfate etc., [31][32][33][34][35][36][37][38][39][40] drug molecules, peptides and polymers. 30,[41][42][43][44][45] In this work, we used CGMD simulations to research the effects of AuNPs with different ligand density, ligand length, and hydrophobicity on PS monolayers at two different area per lipids (APLs).…”

“…This simulation protocol is similar to the one described in our published work. 32,33 The nanoparticles are initially placed in the vacuum close (within $1 nm) to the equilibrated monolayers, as shown in Fig. 2.…”

“…Coarse-grained molecular dynamics (CGMD) simulations have been used to research the structural changes in PS due to the inhalation of different NPs like carbon fullerene, nanotubes, graphene, silica, calcium sulfate etc. , 31–40 drug molecules, peptides and polymers. 30,41–45 In this work, we used CGMD simulations to research the effects of AuNPs with different ligand density, ligand length, and hydrophobicity on PS monolayers at two different area per lipids (APLs).…”

Molecular dynamics simulation insights into the cellular uptake of elastic nanoparticles through human pulmonary surfactant

“…41 While the benets of elasticity adjustment are widely investigated in NPcell interaction, similar studies on the role of elastic NPs penetration on the pulmonary surfactant (PS) monolayer systems are severely lacking and long-overlooked as only a few studies focus on NP permeation processes within PS system without a consideration on the effects of the elasticity variation. [42][43][44][45][46] Therefore, it is of great importance to unveil the underlying mechanisms of the effects of inhaled NPs elasticity on the interaction between NPs and PS monolayer.…”