Tailored Zwitterionic Hemicyanine Reporters for Early Diagnosis and Prognostic Assessment of Acute Renal Failure.
Angew Chem Int Ed Engl
; 62(52): e202315457, 2023 Dec 21.
Article
in En
| MEDLINE
| ID: mdl-37949837
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 ammonium 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 60â
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Acute Kidney Injury
/
Fluorescent Dyes
Limits:
Animals
Language:
En
Journal:
Angew Chem Int Ed Engl
Year:
2023
Document type:
Article
Affiliation country:
China