Tailored Zwitterionic Hemicyanine Reporters for Early Diagnosis and Prognostic Assessment of Acute Renal Failure

Abstract

Drug‐induced renal failure (DIRF) poses a serious medical complication with high mortality risk. However, early diagnosis or prognosis of DIRF remain challenging, as current methods rely on detecting late‐stage biomarkers. Herein we present a library of zwitterionic unimolecular hemicyanines (ZCs) available for constructing activatable reporters to detect DIRF since its initial stage. Zwitterionic properties of these probes are achieved through interspersedly integrating alkyl sulfonates and quaternary ammo‐nium cations onto hemicyanine skeleton, which result in record low plasma protein binding (<5%) and remarkable renal clearance efficiencies (~96%). An activatable reporter ZCRR is further developed by masking the optimal candidate ZC6 with a tetrapeptide specifically cleavable by caspase‐8, an initiating indicator of apoptosis. In living mice with cisplatin‐induced DIRF, systematically administered ZCRR efficiently accumulates in kidneys and responds to elevated caspase‐8 for near‐infrared fluorescence signals ‘turn‐on’, enabling sensitive detection of intrarenal apoptosis 60 h earlier than clinical methods, and precise evaluation of apoptosis remediation effects by different medications on DIRF mice. As it’s urinary excretable, ZCRR also allows for remote detection of DIRF and predicting renoprotective efficacy through in vitro optical urinalysis. This study thus presents unimolecular renal clearable scaffolds that are applicable to developing versatile activatable reporters for renal diseases management.

Recent Progress in Molecular Probes for Imaging of Acute Kidney Injury

“…It also offers potential for remote DIRF detection and prediction of renoprotective efficacy through optical urinalysis. 41…”

“…This enabled sensitive detection of intrarenal apoptosis 60 h earlier than clinical methods, allowing for precise evaluation of apoptosis remediation effects. It also offers potential for remote DIRF detection and prediction of renoprotective efficacy through optical urinalysis …”

Supramolecular engineering cascade regulates NIR-II J-aggregates to improve photodynamic therapy

“…38 Other studies by Zhou and Liu have demonstrated the competitive photodynamic effects of asymmetric NIR-II PSs, suggesting that the asymmetric strategy is a promising approach for designing novel PSs with NIR-II emission. 55,56…”

Early Detection and Noninvasive Staging of Kidney Dysfunction by a PEGylated Conventional Fluorophore via GFR-Sensitive Renal Transport

“…In recent years, the in-depth understanding of the transport and interaction mechanisms of molecules/nanoparticles in the kidney 11,12 NIR fluorescence imaging probes (Table S1), such as ultrasmall gold nanoparticles (GS-AuNPs, 13,14 GNP-KTP5-ICG 15 ) and a series of activatable molecular probes (MRPs, 16 ADR, 17 CDIR2, 18 NCRs, 19 FPRR, 20 1-DPA2, 21 and ACRR 22 ). These probes not only clear rapidly from the kidneys but also have the capability to detect kidney dysfunction with substantially enhanced kidney contrast and minimized background signal interference.…”