Non-disruptive uptake of anionic and cationic gold nanoparticles in neutral zwitterionic membranes

Ester Canepa,Sebastian Salassi,Silvia Dante,Riccardo Ferrando,Annalisa Relini,Giulia Rossi,Fabio Canepa,Ranieri Rolandi,Federica Simonelli,Chiara Lambruschini

doi:10.1038/s41598-020-80953-3

Ester Canepa, Sebastian Salassi + Show 8 more

Open Access

https://doi.org/10.1038/s41598-020-80953-3

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Abstract

The potential toxicity of ligand-protected nanoparticles (NPs) on biological targets is crucial for their clinical translation. A number of studies are aimed at investigating the molecular mechanisms shaping the interactions between synthetic NPs and neutral plasma membranes. The role played by the NP surface charge is still widely debated. We compare, via liposome leakage assays, the perturbation induced by the penetration of sub-6 nm anionic and cationic Au NPs into model neutral lipid membranes composed of the zwitterionic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). Our charged Au NPs are functionalized by a mixture of the apolar 1-octanethiol and a ω-charged thiol which is either the anionic 11-mercapto-1-undecanesulfonate or the cationic (11-mercaptoundecyl)-N,N,N-trimethylammonium. In both cases, the NP uptake in the bilayer is confirmed by quartz crystal microbalance investigations. Our leakage assays show that both negatively and positively charged Au NPs do not induce significant membrane damage on POPC liposomes when penetrating into the bilayer. By means of molecular dynamics simulations, we show that the energy barrier for membrane penetration is the same for both NPs. These results suggest that the sign of the NP surface charge, per se, does not imply different physicochemical mechanisms of interaction with zwitterionic lipid membranes.

Highlights

The potential toxicity of ligand-protected nanoparticles (NPs) on biological targets is crucial for their clinical translation
Liposome leakage assays by Goodman et al.[25], for example, reported the disruptive effects of cationic NPs on negatively charged bilayers composed by a mixture of 1-stearoyl-2-oleoyl-sn-glycero-3-phospho-L-serine (SOPS) and 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC)
We have presented the results of a combined experimental and computational study of the interaction between charged monolayer-protected Au NPs and zwitterionic POPC bilayers

Summary

Introduction

The potential toxicity of ligand-protected nanoparticles (NPs) on biological targets is crucial for their clinical translation. Our charged Au NPs are functionalized by a mixture of the apolar 1-octanethiol and a ω-charged thiol which is either the anionic 11-mercapto-1-undecanesulfonate or the cationic (11-mercaptoundecyl)N,N,N-trimethylammonium In both cases, the NP uptake in the bilayer is confirmed by quartz crystal microbalance investigations. Functionalized Au NPs have become one of the most widely studied NPs for biomedical applications[2,3] Besides biocompatibility, this is due to the unique optical properties of gold which can be exploited both in diagnostic (in vitro sensing and in vivo imaging4,5) and in therapy (delivery a pplications[6,7,8] and plasmonic therapies[8,9,10]). Electrostatic attraction is not a necessary ingredient to the formation of stable NP-bilayer complexes, nor to toxicity, which can take place when the NP and the membrane have a Z-potential of the same s ign[24,28,30]

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