Luminescent ruthenium(II)-containing metallopolymers with different ligands: synthesis and application as oxygen nanosensor for hypoxia imaging

A series of Ru(II)-containing metallopolymers with different polypyridyl complexes, namely [Ru(N<^>N)(2)(L)](PF6)(2) (L = bipyridine-branched polymer; N<^>N = bpy: 2,2 '-bipyridine (Ru 1); phen: 1,10-phenanthroline (Ru 2); dpp: 4,7-diphenyl-1,10-phenanthroline (Ru 3)), were synthesized with the motive that adjusting pi-conjugation length of ligands might produce competent luminescent oxygen probes. The three hydrophobic metallopolymers were studied with H-1 NMR, UV-Vis absorption, and emission spectroscopy, and then were utilized to prepare biocompatible nanoparticles (NPs) via a nanoprecipitation method. Luminescent properties of the NPs were investigated against dissolved oxygen by steady-state and time-resolved spectroscopy respectively. Luminescence quenching of the three NPs all followed a linear behavior in the range of 0-43 ppm (oxygen concentration), but Ru 3-NPs exhibited the highest oxygen sensitivity (82%) and longest emission wavelength (lambda(ex) = 460 nm; lambda(em) = 617 nm). In addition, external interferons from cellular environments (e.g., pH, temperature, and proteins) had been studied on Ru 3-NPs. Finally, dissolved oxygen in monolayer cells under normoxic/hypoxic conditions was clearly differentiated by using Ru 3-NPs as the luminescent sensor, and, more importantly, hypoxia within multicellular tumor spheroids was vividly imaged. These results suggest that such Ru(II)-containing metallopolymers are strong candidates for luminescent nanosensors towards hypoxia.