The present work introduces heterometallic Ag_x-Re₆ (Re₆ = [{Re₆S₈}(OH)_6–n(H₂O)_n]^n–4) nanocrystalline colloids self-generated under the mixing of Re₆ with [Ag₂L₂](BF₄)₂ (L = pyridine-2-ylphospholane) in aqueous solutions. The easy protonation/deprotonation of the Re₆ units incorporated into the Ag_x-Re₆ 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 Re₆ units. The treating of Ag_x-Re₆ by polyethylenimine (PEI) both recharges the colloids and restricts their binding with GSH. Quantitative colocalization analysis of the red emitting Ag_x-Re₆ colloids allows to visualize the low lysosomal trafficking of both initial and PEI-treated colloids, which indicates that pH-driven protonation of either Re₆ 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 [Ag₂L₂](BF₄)₂ and Ag_x-Re₆ colloids, while their PEI-coating changes the cell death mechanism to the non-apoptotic one and enhances the cytotoxicity.