Noninvasive Detection of Chorioretinal Hypoxia via Poly(lactic-co-glycolic acid) Nanoparticles Embedded with Purely Organic Phosphors

Ischemia-induced hypoxia is a critical complication in retinal diseases, leading to significant vision impairment and blindness due to disrupted blood flow and oxygen delivery. Currently, there is no effective method to assess oxygen levels in extravascular retinal tissue. Traditional hypoxia detection methods, such as oxygen-sensitive microelectrodes, magnetic resonance imaging, and retinal oximetry, have limitations including invasiveness, low spatial resolution, and lack of real-time monitoring. Herein, a noninvasive hypoxia detection method is proposed by utilizing lipid-polymer nanoparticles (NPs) with purely organic room-temperature phosphorescence materials for real-time detection with high spatial and temporal resolution. To enhance biocompatibility and efficacy, NPs were fabricated using biodegradable poly(lactic-co-glycolic acid) (PLGA) and SeCO as a phosphor. PLGA degrades into nontoxic by-products, while the excitation wavelength of SeCO at 393 nm minimizes damage from short wavelengths and enhances tissue penetration. Furthermore, the NPs’ size is optimized to improve cellular uptake and reduce bodily accumulation, as smaller NPs are preferred for biocompatibility. Herein, synthesis, characterization, and evaluation of these PLGA-based phosphorescent NPs in rabbit models of retinal vein occlusion and choroidal vascular occlusion are involved. This approach represents a significant advancement in noninvasive biomedical imaging, improving the diagnosis and management of ischemic retinal diseases.