Aromaticity/Bulkiness of Surface Ligands to Promote the Interaction of Anionic Amphiphilic Gold Nanoparticles with Lipid Bilayers

Abstract

The presence of large hydrophobic aromatic residues in cell-penetrating peptides or proteins has been demonstrated to be advantageous for their cell penetration. This phenomenon has also been observed when AuNPs were modified with peptides containing aromatic amino acids. However, it is still not clear how the presence of hydrophobic and aromatic groups on the surface of anionic AuNPs affects their interaction with lipid bilayers. Here, we studied the interaction of a range of anionic amphiphilic AuNPs coated by different combinations of hydrophobic and anionic ligands with four different types of synthetic lipid vesicles. Our results demonstrated the important role of the surface aromatic or bulky groups, relative to the hydrocarbon chains, in the interaction of anionic AuNPs with lipid bilayers. Hydrophobic interaction itself arising from the insertion of aromatic/bulky ligands on the surface of AuNPs into lipid bilayers is sufficiently strong to cause overt disruption of lipid vesicles and cell membranes. Moreover, by comparing the results obtained from AuNPs coated with aromatic ligands and cyclohexyl ligands lacking aromaticity respectively, we demonstrated that the bulkiness of the terminal groups in hydrophobic ligands instead of the aromatic character might be more important to the interaction of AuNPs with lipid bilayers. Finally, we further correlated the observation on model liposomes with that on cell membranes, demonstrating that AuNPs that are more disruptive to the more negatively charged liposomes are also substantially more disruptive to cell membranes. In addition, our results revealed that certain cellular membrane domains that are more susceptible to disruption caused by hydrophobic interactions with nanoparticle surfaces might determine the threshold of AuNP-mediated cytotoxicity.

Supramolecular Control of Azobenzene Switching on Nanoparticles

“…However, cofunctionalization of NPs with mixtures of polar and apolar ligands is not an easy task: earlier studies showed that such processes typically result in preferential adsorption of only one of the two ligands. Among numerous other examples, − Bishop and co-workers found that performing ligand exchange on DDA-capped 6 nm Au NPs with an 8:1 mixture of octadecanethiol and ω-mercaptoundecanoic acid resulted in a 0.35:1 mixture of these two ligands on the functionalized NPs, whereas Meli et al reported that a 3:1 molar ratio of dodecanethiol and ω-mercaptoundecanol used to functionalize 4 nm NPs was increased up to 32:1 as a result of the ligand exchange reaction . The discrepancy between the solution and the on-NP ratio typically originates from attractive/repulsive interactions between the ligands or when one of the ligands induces NP precipitation during the functionalization process.…”

Sterically encumbered 2,6-dibenzhydryl-4-methylphenyl derived ligand systems: synthesis and structures

“…Incorporation of sterically bulky ligands into metal complexes is a well explored but ever growing field due to the fact that the steric bulk of the ligand facilitates the fine-tuning of physical and chemical properties of the complexes. [1][2][3][4][5][6] This feature is highly pivotal specially in tailoring activity and selectivity of catalytically active complexes [7][8][9][10] as well as for the synthesis and stabilization of low-valent metal complexes. [11][12][13][14][15] Among these, bulky Schiff base derivatives are of special importance due to their ease of synthesis and strong affinity of the imino-nitrogen for most of the metal systems.…”

Rupture of Lipid Membranes Induced by Amphiphilic Janus Nanoparticles

“…Exploring the role that particle surface coatings have on these interactions is of central importance. For particles with uniform surface chemistry, surface properties such as charge, − hydrophobicity, − and adsorbed protein corona − have been shown to play pivotal roles in determining their interaction with biomembranes. Much less is known about the effects of heterogeneous surface chemistry.…”