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

Abstract

In the present report we describe block copolymer micelles based on either poly(dimethylsiloxane-block-ethylene glycol), PDMS15-b-PEG110, or poly(ε-caprolactone-block-ethylene glycol), PCL45-b-PEG110, loaded by the near-infrared (NIR) phosphorescent iridium(III) complex (Ir1) of [(N^C)2Ir(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 ([email protected]15-b-PEG110 and [email protected]45-b-PEG110) with aggregate-free non-covalent adducts of Ir1 with human serum albumin ([email protected]). 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 [email protected] does not exceed 27% resulting in highest possible loading of 0.35 wt.% and much lower luminescence intensity. Lifetime measurements revealed that [email protected]45-b-PEG110 micelles are the best in protecting Ir1 from interactions with the components of physiological media while [email protected]15-b-PEG110 demonstrates the highest lifetime response towards oxygen variations (τdeg/τaer = 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.