“Proton sponge” effect and apoptotic cell death mechanism of Agx-Re6 nanocrystallites derived from the assembly of [{Re6S8}(OH)6–n(H2O)n]^n–4 with Ag⁺ ions

The present work introduces heterometallic Ag x -Re 6 (Re 6 = [{Re 6 S 8 }(OH) 6– n (H 2 O) n ] n –4 ) nanocrystalline colloids self-generated under the mixing of Re 6 with [Ag 2 L 2 ](BF 4 ) 2 (L = pyridine-2-ylphospholane) in aqueous solutions. The easy protonation/deprotonation of the Re 6 units incorporated into the Ag x -Re 6 colloids provides their negative surface charging and low aggregation in neutral buffered solutions and the recharging of the colloids in weak acidic solutions modeling lysosomal environment. The surface-exposed Ag(I) ions are prerequisite for binding of glutathione (GSH), which is visualized through the red emission of the Re 6 units. The treating of Ag x -Re 6 by polyethylenimine (PEI) both recharges the colloids and restricts their binding with GSH. Quantitative colocalization analysis of the red emitting Ag x -Re 6 colloids allows to visualize the low lysosomal trafficking of both initial and PEI-treated colloids, which indicates that pH-driven protonation of either Re 6 or amino-groups of PEI provides the similar “proton sponge” effects. The apoptotic assay results indicate high contribution of the apoptotic cell death mechanism for both [Ag 2 L 2 ](BF 4 ) 2 and Ag x -Re 6 colloids, while their PEI-coating changes the cell death mechanism to the non-apoptotic one and enhances the cytotoxicity. • pH- and ligand-assisted engineering of Ag x -Re 6 nanocrystallites in aqueous solutions. • Counterion-induced deprotonation of Re 6 units provides colloid stability of Ag x -Re 6. • Protonation of Re 6 units in Ag x -Re 6 at pH < 5.0 generates luminescence response. • “Proton sponge” effect of Ag x -Re 6 colloids explains their low lysosomal trafficking. • Ag + -centers of Ag x -Re 6 induce apoptotic pathway of the cancer cells death.