Intracellular Oxygen Sensors Based on Block Copolymer Micelles Loaded With Phosphorescent Ir( <scp>III</scp> ) and Pt( <scp>II</scp> ) Complexes

ABSTRACT Polymer micelles are established nanocarriers for hydrophobic molecules, but their use as hosts for sensors of physiological parameters remains underexplored. This work investigates the incorporation of phosphorescent transition metal complexes into block copolymer micelles and examines how composition and structure affect micellar stability and photophysical properties. The study also evaluates their potential as a novel class of oxygen nanosensors with lifetime‐based response. Micelles are prepared from block copolymers of poly(ethylene glycol) (PEG) with diverse hydrophobic blocks: polystyrene (PS 35 ‐ b ‐PEG 115 ), poly(methyl methacrylate) (PMMA 55 ‐ b ‐PEG 95 ), polybutadiene (PBd 90 ‐ b ‐PEG 115 ), polydimethylsiloxane (PDMS 15 ‐ b ‐PEG 115 ), and polycaprolactone (PCL 45 ‐ b ‐PEG 115 ). Six phosphorescent complexes, including three Pt(II) and three Ir(III) species, serve as payloads. Screening of “complex@block copolymer” pairs based on sedimentation stability, phosphorescence decay, and oxygen sensitivity identifies Ir3 @PCL 45 ‐ b ‐PEG 115 loaded with 2 wt.% of Ir3 as the optimal biosensing system. For this system, loading efficiency, size distribution, cross‐sensitivity to environmental parameters, Stern–Volmer plots, and MTT cytotoxicity are assessed. Confocal microscopy and phosphorescence lifetime imaging microscopy (PLIM) demonstrate efficient internalization into CHO‐K1 and HeLa cells. The sensor shows distinct lifetime responses under hypoxic, normoxic, and intermediate oxygenation, enabling quantitative intracellular oxygen sensing with pO 2 resolution of 35–40 mm Hg in both cell monolayers and suspensions.