Physiologically Robust Ultralong Aqueous Phosphorescence With Quantitative Hypoxia Sensing Through Hydrophobic‐Hydrophilic Engineering

ABSTRACT

Organic room‐temperature phosphorescence (RTP) materials hold great promise as bioimaging agents due to their long‐lived emission and high signal‐to‐background ratios. However, their application in physiological environments is often hampered by water‐induced quenching. Herein, we report a ternary‐component nanoengineering strategy featuring a precisely engineered hydrophobic–hydrophilic architecture that enables bright, color‐tunable, and long‐lived RTP in aqueous media. The optimized 1,2‑PhCS@PLA nanoparticles achieve an ultralong phosphorescence lifetime of 1.04 s, the longest reported for aqueous organic RTP systems to date, and retain robust afterglow under physiological conditions with persistent RTP exceeding 12 s at 310 K (close to body temperature). This outstanding performance is enabled by a multifunctional hydrophobic layer that (1) protects triplet excitons from water, (2) suppresses nonradiative decay through matrix rigidity, and (3) allows dynamic oxygen responsiveness via its porous nature. These features enable quantitative in vitro hypoxia detection and high‐contrast afterglow imaging of tumor hypoxia in living mice, achieving a signal‐to‐background ratio up to 221. This work establishes a foundation for advanced phosphorescent biosensors and biomedical imaging applications.