Structure impact on photodynamic therapy and cellular contrasting functions of colloids constructed from dimeric...

Electrostatically driven self-assembly of [Au₂L₂]²⁺ (L is cyclic PNNP ligand) with [{Mo₆I₈}(L')₆]^2- (L' = I^-, CH₃COO^-) in aqueous solutions is introduced as facile route for combination of therapeutic and cellular contrasting functions within heterometallic colloids (Mo₆-Au₂). The nature of L' affects the size and aggregation behavior of crystalline Mo₆-Au₂ aggregates, which in turn affect the luminescence of the cluster units incorporated into Mo₆-Au₂ colloids. The spin trap facilitated electron spin resonance spectroscopy technique indicates that the level of ROS generated by Mo₆-Au₂ colloids is also affected by their size. Both (L' = I^-, CH₃COO^-) Mo₆-Au₂ colloids undergo cell internalization, which is enhanced by their assembly with poly-DL-lysine (PL) for L' = CH₃COO^-, but remains unchanged for L' = I^-. The colloids PL-Mo₆-Au₂ (L' = CH₃COO^-) are visualized as huge crystalline aggregates both outside and inside the cell cytoplasm by confocal microscopy imaging of the incubated cells, while the smaller sized (30-50 nm) PL-Mo₆-Au₂ (L' = I^-) efficiently stain the cell nuclei. Quantitative colocalization analysis of PL-Mo₆-Au₂ (L' = CH₃COO^-) in lysosomal compartments points to the fast endo-lysosomal escape of the colloids followed by their intracellular aggregation. The cytotoxicity of PL-Mo₆-Au₂ differs from that of Mo₆ and Au₂ blocks, predominantly acting through apoptotic pathway. The photodynamic therapeutic effect of the PL-Mo₆-Au₂ colloids on the cancer cells correlates with their intracellular trafficking and aggregation.