Au₂₅(SC_nH_2n+1)₁₈ Clusters in Biomimetic Membranes: Role of Size, Charge, and Transmembrane Potential in Direct Membrane Permeation

Gold nanoclusters and nanoparticles are promising materials for applications in nanomedicine, and therefore, understanding their interaction with cell membranes is of particular importance. A series of neutral and anionic Au25(SCnH2n+1)18 monolayer protected clusters (MPCs) (briefly, Cn0 and Cn– clusters), was embedded into two types of biomimetic membranes supported by mercury electrodes. The first was a dioleoylphosphatidylcholine (DOPC) self-assembled monolayer (SAM), whereas the second was a tethered bilayer lipid membrane (tBLM) obtained by first anchoring a thiolipid monolayer to the mercury surface and then self-assembling a DOPC monolayer on top of it. The diameter of these clusters, from 1.7 to 2.7 nm depending on the thiolate ligand, is smaller than the thickness of biomembranes and biomimetic membranes. Both neutral and anionic Au25(SCnH2n+1)18 MPCs can penetrate the lipid bilayer moiety of the tBLM, without disrupting it; in particular, anionic Au25 clusters require positive transmembrane potentials to do so. Neutral Au25 clusters exchange one electron with mercury in a DOPC SAM, where they can come in contact with the mercury surface, whereas they are prevented from doing so at the tBLM because of their inability to cross the hydrophilic chain separating the lipid bilayer moiety from the mercury surface. The potential of these Au25 clusters to penetrate directly the plasma membrane is particularly convenient for targeted drug delivery. They are highly stable, biocompatible, and catalytic, and their uniform size is of importance in nanomedicine. Moreover, they may induce an efficient energy transfer to 3O2, allowing applications in radiotherapy and antimicrobial activity.