In this study, we demonstrate structural variation at the molecular, supramolecular and nanoscale levels as a tool for modifying the anticancer activity of alkynyl (C ≡ CR') Au(I) complexes with P2N2 (1,5-diaza-3,7-diphosphacyclooctane) ligands. The molecular structure is varied in a series of newly synthesized five Au(I) complexes with different substituents in the P2N2 and C ≡ CR' ligands, respectively. Due to the low solubility of these complexes in water, they were transformed into hydrophilic colloids using two different approaches, thus resulting in the formation of either core-shell, where the complexes aggregate to form solid cores, or micellar nanoparticles (NPs), in which the complexes are incorporated into a non-polar micellar core. The hydrophilic surface of both types of NPs is due to either aggregation of Pluronic F127 or its mixed aggregation with Pluronic P123. Incorporation of the complexes into the non-polar core of micelles can be considered as a more effective way to ensure their stability in an aqueous environment compared to the inclusion of these complexes into a solid core. It has been shown that Au(I) alkynyl complexes exhibit lower anticancer activity when incorporated into solid cores compared to Pluronic micelles. Moreover, the anticancer activity of these complexes can be further enhanced by altering the structure of the Pluronic components in the micelles. The achieved anticancer activity of the complexes does not correlate with the level of intracellular reactive oxygen species (ROS) formation. This suggests that altering the properties of Pluronic-based micelles can be considered a powerful tool for modifying the anticancer activity of the Au(I) complexes within them. © 2026 Elsevier B.V.