Ischemia-induced hypoxia is a common complication associated with numerous diseases and is the most important prognostic factor in retinal vein occlusions (RVOs). Early detection and long-term visualization of retinal tissue hypoxia is essential to understand the pathophysiology and treatment of ischemic retinopathies. However, no effective solution exists to evaluate extravascular retinal tissue oxygen tension. Here, we demonstrate a lipid-polymer hybrid organic room-temperature phosphorescence (RTP) nanoparticle (NP) platform that optically detects tissue hypoxia in real-time with high signal-to-noise ratio. The fabricated NPs exhibit long-lived bright RTP, high sensitivity toward oxygen quenching, and desirable colloidal and optical stability. When tested as a hypoxia imaging probe in vivo using rabbit RVO and choroidal vascular occlusion (CVO) models via intravitreal and intravenous (IV) injections, respectively, its RTP signal is exclusively turned on where tissue hypoxia is present with a signal-to-noise ratio of 12.5. The RTP NP platform is compatible with multimodal imaging. No ocular or systemic complications are observed with either administration route. The developed organic RTP NPs present a novel platform approach that allows for biocompatible, nondestructive detection of tissue hypoxia and holds promise as a sensitive imaging tool to monitor longitudinal tissue oxygen levels and evaluate various hypoxia-driven vascular diseases.
Keywords: hypoxia; ischemia; lipid-polymer hybrid nanoparticles; nondestructive tissue hypoxia detection; purely organic room-temperature phosphorescent nanosensor; retinal imaging; retinal vein occlusion.