A Renally Clearable Activatable Polymeric Nanoprobe for Early Detection of Hepatic Ischemia-Reperfusion Injury

Although hepatic ischemia-reperfusion injury (IRI) represents a major complication in many clinical settings, it remains a diagnostic dilemma due to its reliance on insensitive assays or invasive biopsy. The development of an activatable polymeric nanoprobe (APN_SO) for real-time in vivo near-infrared fluorescence (NIRF) imaging and urinalysis of hepatic IRI is reported here. APN_SO has a backbone comprising renally clearable fluorophore fragments and self-immolative structural units. In the presence of an oxidative stress biomarker (superoxide anion, O₂^•−) during hepatic IRI, APN_SO can be fluorescently activated for in vivo NIRF imaging and depolymerized to release renally clearable fluorophores for urinalysis. By virtue of its high hepatic accumulation, sensitive response toward O₂^•−, and effective release of renally clearable fluorophores, APN_SO-based imaging and urinalysis detect hepatic IRI at least 7 h earlier than typical clinical assays in a mouse model. This study not only provides new opportunities for noninvasive diagnosis of hepatic IRI, but also reveals guidelines for the development of optical nanosensors for early urinalysis.