Abstract
Purpose :
Ischemia-induced hypoxia is a common complication associated with numerous diseases including retinal vein occlusions. No effective solution exists to evaluate extravascular tissue oxygen tension. This report demonstrates a novel 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.
Methods :
A lipid-polymer hybrid, core-shell RTP NP was fabricated with Br6A metal-free organic phosphor embedded within the polymer matrix core coated with an amphiphilic lipid shell. Poly(4-bromostyrene) (PS4Br) was chosen as the host polymer for intravitreal injection (Br6A-LPS4Br) and polystyrene-b-poly(4-vinylpyridine) (PS4VP) for intravenous injection. This was injected into 11 rabbits with a Rose Bengal dye-enhanced thrombosis retinal vein occlusion model, laser photocoagulation, or controls and evaluated with multimodal imaging post NP administration via intravenous and intravitreal administration.
Results :
The fabricated RTP NPs exhibit bright RTP and high sensitivity toward oxygen quenching with desirable colloidal and optical stability. The RTP NPs were tested as a hypoxia imaging probe in vivo using rabbit RVO and photocoagulation models via intravitreal and intravenous injection respectively. The RTP NP signal is exclusively generated where tissue hypoxia is present with a signal-to-noise ratio of 12.5. Longitudinal phosphorescence imaging in Rose-Bengal RVO and control rabbits demonstrated significant phosphorescent signal peaking at 2h post-intravitreal injection of NP that persisted for at least 7 days (Figure). No ocular or systemic complications are observed with either administration route.
Conclusions :
This organic RTP NPs allows for biocompatible, non-destructive, sensitive detection of tissue hypoxia longitudinally and has potential to evaluate hypoxia-driven retinal vascular diseases.
This is a 2021 ARVO Annual Meeting abstract.