Abstract
Purpose :
Ischemia-induced hypoxia is a common complication associated with numerous diseases including retinal vein occlusions (RVO). No effective solution exists to evaluate extravascular tissue oxygen tension. This report demonstrates a novel metal-free purely organic room-temperature phosphorescent (POP) nanoparticle (NP) platform that optically detects eye hypoxia in real-time with high signal-to-noise ratio.
Methods :
POP nanosensor was fabricated through a single-step nanoprecipitation method with the oxygen-sensitive POP encapsulated in an oxygen-permeable and biodegradable polymer matrix, poly(lactic-co-glycolic acid) (PLGA), forming the polymeric core of the NP. This POP NP was injected intravenously into 6 rabbits with a Rose Bengal dye-enhanced thrombosis RVO model or controls and evaluated with multimodal imaging (color fundus photography, fluorescein angiography, and phosphorescence imaging) post 4mL intravenous POP NP administration (2.5 mg/mL).
Results :
Longitudinal distribution of the POP NPs was monitored at different time points (15 min, 1, 2, 4, 8, and 24 hours, and 1, 3, 7, 10, 17, 21, and 28 days). Figures 1 illustrates the color fundus images of two different sides of the same rabbit eye: the hypoxic RVO side and the normoxic control side. There was no phosphorescent signal observed on the image before the injection of POP NP or on the untreated control side. The NPs are clearly visualized starting at 15 min post-injection and is still visible up to 7 days post-injection on the hypoxic side. Average phosphorescence intensity was quantified for each time point and peaked at 120 at 15 minutes post-injection. These results were stable and reproducible in 6 rabbits. No ocular or systemic complications were observed.
Conclusions :
POP NPs allow for biocompatible, non-destructive, sensitive detection of tissue hypoxia longitudinally and have the potential to evaluate hypoxia-driven retinal vascular diseases.
This abstract was presented at the 2024 ARVO Imaging in the Eye Conference, held in Seattle, WA, May 4, 2024.