Supramolecularly Engineered Reporters with Superoxide Anion‐Triggered Chemiluminescence for Early Diagnosis and Efficient Amelioration of Acute Kidney Injury

We report the “water‐in‐oil‐in‐water” preparation of kidney injury molecule‐1‐targeting supramolecular chemiluminescence (CL) reporters (PCCS), consisting of L‐serine‐modified poly(lactic‐co‐glycolic) acid (PLGA)‐encapsulated peroxyoxalate (CPPO), chlorin e6 (Ce6) and superoxide dismutase (SOD), for...

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Bibliographic Details
Published in:Angewandte Chemie 2023-07, Vol.135 (29), p.n/a
Main Authors: Wu, Menglin, Cui, Mingyue, Jiang, Airui, Sun, Rong, Liu, Mingzhu, Pang, Xueke, Wang, Houyu, Song, Bin, He, Yao
Format: Article
Language:English
Subjects:
Acute Kidney Injury
Biomarkers
Chemiluminescence
Chemiluminescence Reporters
Chemistry
Diagnosis
Energy transfer
Glutathione
Inflammation
Inflammatory response
Injuries
Kidneys
Oxidation
Polylactide-co-glycolide
Serine
Signal transduction
Superoxide Anion Detection
Superoxide anions
Superoxide dismutase
Transcriptomics
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Summary:We report the “water‐in‐oil‐in‐water” preparation of kidney injury molecule‐1‐targeting supramolecular chemiluminescence (CL) reporters (PCCS), consisting of L‐serine‐modified poly(lactic‐co‐glycolic) acid (PLGA)‐encapsulated peroxyoxalate (CPPO), chlorin e6 (Ce6) and superoxide dismutase (SOD), for early diagnosis and amelioration of acute kidney injury (AKI). In this system, O2⋅−, a biomarker of AKI, triggers the oxidation of CPPO to 1,2‐dioxetanedione and subsequent CL emission via CL resonance energy transfer to Ce6. The L‐serine‐modified PLGA stabilizes CPPO and Ce6 via noncovalent interactions, promoting long‐lived CL (half‐lives: ≈1000 s). Transcriptomics analysis shows that PCCS reporters reduce the inflammatory response through glutathione metabolism and inhibition of the tumor necrosis factor signaling pathway. The reporters are able to non‐invasively detect AKI at least 12 h earlier than current assays, and their antioxidant properties allow simultaneous treatment of AKI. Supramolecularly engineered chemiluminescence reporters (PCCS), consisting of L‐serine‐modified PLGA‐encapsulated peroxyoxalate, chlorin e6 and superoxide dismutase, are reported. The PCCS reporters were applied for the simultaneous diagnosis and treatment of acute kidney injury.
ISSN:0044-8249
1521-3757
DOI:10.1002/ange.202303997