ABSTRACT
Gold(I) complexes of LAu2Cl2 composition based on P2N2 ligands, namely 1,5-diaza-3,7-diphosphacyclooctanes, containing ethylpyridyl substituents at the phosphorus atoms and sp2- or sp3-hybridized endocyclic nitrogen atoms were synthesized. The SCXRD analysis indicated the strong impact of the geometry of the nitrogen atom on the structure and conformational flexibility of the complexes. The N-aryl substituted ligand with the planar endocyclic nitrogen atom provides higher flexibility of the complex and an ability to bind the solvent molecules in the "host-guest" mode, whereas that kind of behavior is forbidden for the complex with an N-alkyl substituted ligand with a pyramidal nitrogen atom. The substituents at nitrogen atoms also control the origin of the emission, which is phosphorescence for the N-aryl substituted complex and fluorescence for the N-alkylaryl substituted complex. The phosphorescent gold(I) complex displays high cytotoxicity without selectivity toward the m-HeLa and normal cells, but the core-shell nanoparticles formed on the base of the complex demonstrate reduced cytotoxicity. The luminescence of the NPs allows tracking the complexes in the cell samples.
ABSTRACT
The work presents core-shell nanoparticles (NPs) built from the novel Cu(I) complexes with cyclic P2N2-ligands (1,5-diaza-3,7-diphosphacyclooctanes) that can visualize their entry into cancer and normal cells using a luminescent signal and treat cells by self-enhancing generation of reactive oxygen species (ROS). Variation of P- and N-substituents in the series of P2N2-ligands allows structure optimization of the Cu(I) complexes for the formation of the luminescent NPs with high chemical stability. The non-covalent modification of the NPs with triblock copolymer F-127 provides their high colloidal stability, followed by efficient cell internalization of the NPs visualized by their blue (â450 nm) luminescence. The cytotoxic effects of the NPs toward the normal and some of cancer cells are significantly lower than those of the corresponding molecular complexes, which correlates with the chemical stability of the NPs in the solutions. The ability of the NPs to self-enhanced and H2O2-induced ROS generation is demonstrated in solutions and intracellular space by means of the standard electron spin resonance (ESR) and fluorescence techniques correspondingly. The anticancer specificity of the NPs toward HuTu 80 cancer cells and the apoptotic cell death pathway correlate with the intracellular level of ROS, which agrees well with the self-enhancing ROS generation of the NPs. The enhanced level of ROS revealed in HuTu 80 cells incubated with the NPs can be associated with the significant level of their mitochondrial localization.
ABSTRACT
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.
