Original Article
Ligand-lipid and ligand-core affinity control the interaction of gold nanoparticles with artificial lipid bilayers and cell membranes

https://doi.org/10.1016/j.nano.2015.12.384Get rights and content

Abstract

Interactions between nanoparticles (NPs) and biomembranes depend on the physicochemical properties of the NPs, such as size and surface charge. Here we report on the size-dependent interaction of gold nanoparticles (AuNPs), stabilized with ligands differing in charge, i.e. sodium 3-(diphenylphosphino)benzene sulfonate (TPPMS) and sodium 3,3′,3″-triphenylphosphine sulfonate (TPPTS), respectively, with artificial membranes (black lipid membranes; BLMs) and HeLa cells. The TPPTS-stabilized AuNPs affect BLMs at lower size than TPPMS-stabilized ones. On HeLa cells we found decreasing cytotoxicity with increasing particle size, however, with an overall lower cytotoxicity for TPPTS-stabilized AuNPs. We attribute size-dependent BLM properties as well as reduced cytotoxicity of TPPTS-stabilized AuNPs to weaker shielding of the AuNP core when stabilized with TPPTS. We hypothesize that the partially unshielded hydrophobic gold core can embed into the hydrophobic membrane interior. Thereby we demonstrate that ligand-dependent cytotoxicity of NP can occur even when the NPs are not translocated through the membrane.

From the Clinical Editor

The use of nanoparticles (NPs) in the clinical setting means that there will be interactions between NPs and cell membranes. The authors investigated the underlying processes concerning cellular uptake and potential toxicity of gold nanoparticles (AuNPs) using particles with ligands different sizes and charges. The findings should further enhance existing knowledge on future design of safer NPs in the clinic.

Graphical Abstract

Ligand-nanoparticle interactions control nanoparticle embedding in lipid membranes

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Section snippets

Syntheses

AuTPPCl was synthesized by using the protocol of Reed et al33 (details for all NP see supplemental information). Triphenylphosphine-3-monosulfonic acid (TPPMS) was prepared according to Ahrland et al.34 Au1.4TPP was synthesized by a method of Schmid et al.35 For synthesis of 5 nm sized colloidal AuNPs HAuCl4 was reduced with NaBH4 in adaption to Selvakannan et al.36 Synthesis of about 10 nm sized colloidal AuNPs was performed by a citrate reduction of HAuCl4 according to Olmedo et al.37 For

Nanoparticle syntheses and characterization

Different routes were followed to synthesize TPPMS- or TPPTS-stabilized (Figure 1) AuNPs with varying sizes. The TPPMS-stabilized AuNPs with diameters of 1.4 nm and 15 nm were used in several earlier studies where the syntheses and the analytical data are described.26, 27, 39 To investigate the interactions of AuNPs in the size range of 5-12 nm, new TPPMS- as well as TPPTS-stabilized AuNPs were synthesized (see Methods and SI). Characterization with dynamic light scattering (DLS) depicts that for

Discussion

In order to compare the results obtained on lipid bilayer membranes with actual cell membranes, we have tested the above described AuNPs regarding their cytotoxicity toward HeLa cervix carcinoma epithelial cells (see SI for methods). In an earlier study we have shown for TPPMS-stabilized particles that Au1.4MS is the most cytotoxic species. Smaller particles as well as 15 nm sized TPPMS-stabilized particles were found to be less toxic.26 In this work we analyze whether besides the particle size

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    JS and WW acknowledge support by the BMBF project “Molecular Interaction Engineering” in the program Biotechnology 2020 + and the program Science and Technology of Nanosystems at KIT. JB and US acknowledge support by the German Research Foundation DFG (Investigator Grants Si609/9 and Research Training Group “Biointerface”) as well as by the Excellence Initiative of the German federal and state Governments (I3TM).

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    The authors have equally contributed to this work.

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