Design of Fluorinated Peptides as Biotransformed Urinalysis Biomarkers for Non‐Invasive Diagnosis and Treatment of Liver Injury through Enzyme Directed Kinetics

Urinalysis, as a non-invasive and efficient diagnostic method, is very important but faces great challenges due to the complex compositions of urine and limited naturally occurring biomarkers for diseases. Herein, by leveraging the intrinsic absence of endogenous fluorinated interference, a strategy with the enzymatically activated assembly of synthetic fluorinated peptide for cholestatic liver injury (CLI) diagnosis and treatment through ¹⁹F nuclear magnetic resonance (NMR) urinalysis and efficient drug retention is developed. Specifically, alkaline phosphatase (ALP), overexpressed in the liver of CLI mice, triggers the assembly of fluorinated peptide, thus, directing the traffic and dynamic distribution of the synthetic biomarkers after administration, whereas CLI mice display much slower clearance of peptides through urine as compared with healthy counterparts. As such, it enables to transform pathophysiological information into exogenous signals via noninvasive urinary monitoring. Moreover, as a proof-of-concept, by grafting different functional groups to peptides, the theranostic platforms can be established to provide a new paradigm for the design of multifunctional peptides.