Fluorescent Lipid Nanoparticles as Biomembrane Models for Exploring Emerging Contaminant Bioavailability Supported by Density Functional Theory Calculations

Abstract

[eng] Experimental sensing schemes and thermodynamic <em>in-silico</em> studies are combined holistically in this manuscript so as to give new insights into the bioavailability of environmental contaminants via permeation across lipid nanoparticles (liposomes) as a mimicry of biological membranes. Using Prodan and Laurdan as fluorescent membrane probes, phosphatidylcholine-based unilamellar liposomes are harnessed to investigate membranotropic effects of alkyl esters of p-hydroxybenzoic acid and triclosan <em>in-vitro</em> on the basis of steady-state fluorescence anisotropy, light scattering and generalized polarization measurements. The feasibility of the analytical responses to ascertain differences in temperature-dependent contaminant bioavailability is investigated in detail. High level density functional theory (DFT) calculations (RI-BP86-D3/def2-SVP) have been resorted to investigate non-covalent 1:1 complexes of the fluorescent probes and emerging contaminants with dipalmitoylphosphatidylcholine, as a minimalist model of a lipid nanoparticle, to evaluate both the interaction energies and the geometries of the complexes. This information can be related to the degree of penetration of the guest across the lipid bilayer. Our experimental results supported by <em>in-silico</em> DFT calculations and ecotoxicological data let us to conclude that simple analytical measurements of liposomal changes in lipid packaging, permeability and fluidity are appropriate to foresee the potential bioavailability and toxicity of emerging contaminants.