Lifetime oxygen sensors based on block copolymer micelles and non-covalent human serum albumin adducts bearing phosphorescent near-infrared iridium(III) complex

• Amphiphilic block copolymer micelles are loaded with hydrophobic iridium(III) complex. • The iridium chromophore in micelles displays NIR phosphorescence sensitive to O 2 . • Polymer micelles lifetime response may be used for oxygen sensing using PLIM. • Phosphorescent micelles readily internalize into Chinese hamster ovary cells. In the present report we describe block copolymer micelles based on either poly(dimethylsiloxane- block -ethylene glycol), PDMS 15 - b -PEG 110 , or poly(ε-caprolactone- block -ethylene glycol), PCL 45 - b -PEG 110 , loaded by the near-infrared (NIR) phosphorescent iridium(III) complex ( Ir1 ) of [(N^C) 2 Ir(N^N)] + type, where N^C is cyclometalating 6-(benzo[b]thiophen-2-yl)phenanthridine ligand and N^N is a bidentate diimine (1-(pyridin-2-yl)-1H-1,2,3-triazol-4-yl)methyl benzoate) ligand. We also compare both types of phosphorescent micelles ( Ir1@PDMS 15 - b -PEG 110 and Ir1@PCL 45 - b -PEG 110 ) with aggregate-free non-covalent adducts of Ir1 with human serum albumin ( Ir1@HSA ). Finally, we evaluate the applicability of all these phosphorescent nanoparticles for oxygen sensing by phosphorescence lifetime imaging (PLIM). Both studied block copolymer micelles are compact (hydrodynamic radii less than 20 nm) and solubilize Ir1 up to at least 8 wt.% with almost 100% loading efficiency while preserving the complex phosphorescence. In contrary, the loading efficiency of Ir1 in Ir1@HSA does not exceed 27% resulting in highest possible loading of 0.35 wt.% and much lower luminescence intensity. Lifetime measurements revealed that Ir1@PCL 45 - b -PEG 110 micelles are the best in protecting Ir1 from interactions with the components of physiological media while Ir1@PDMS 15 - b -PEG 110 demonstrates the highest lifetime response towards oxygen variations (τ deg /τ aer = 2.5), the fastest internalization into Chinese hamster ovary (CHO-K1) cell monolayers, and the strongest intracellular PLIM signal. Though neither system showed ideal combination of desired properties, the present study clearly demonstrates high potential of phosphorescent block copolymer micelles in PLIM oxygen sensing.