Affiliation:
1. School of Pharmaceutical Sciences Sun Yat-sen University 510006 Guangzhou China
2. National-Local Joint Engineering Laboratory of Druggability and New Drugs Evaluation Guangdong Provincial Key La-boratory of New Drug Design and Evaluation Sun Yat-sen University 510006 Guangzhou China
3. Department of Radiation Oncology Stanford University School of Medicine CA 94305 Stanford USA
Abstract
AbstractChemiluminescence imaging has been recognized as a valuable tool for ultrasensitive detection of physio‐pathological events through elimination of background autofluorescence. However, most chemiluminescent nanoprobes suffer from shallow imaging depths and slow clearance from living bodies, which impede their use in clinical settings. We herein report size‐transformable nanoreporters (ADN1 and ADN2) that could be activated at disease site by superoxide anion (O2⋅−) to trigger nanostructure disassembly into renal excretable fluorescent fragments as well as chemiluminescence turn‐on for crosstalk‐free duplex chemo‐fluorescence imaging and in vitro urinalysis. In peritonitis mouse model, we demonstrate that the representative nanoreporter ADN1 spontaneously accumulates at the disrupted peritoneum and is cleaved by upregulated O2⋅− to initiate depolymerization and result in red chemiluminescence at 620 nm, enabling sensitive detection of peritonitis at least 19 h earlier than gold standard histological assays. Additionally, the incorporation of a near‐infrared (NIR) dye into ADN1 results in ADN2 exhibiting intense and red‐shifted chemiluminescence at ≈800 nm, which permits early detection of deeply seated diseases such as drug‐induced hepatotoxicity. This study thus showcases a modular design strategy that is not only applicable to developing versatile chemiluminescent nanoprobes with switchable pharmacokinetics for early disease diagnosis, but also promising for future clinical translations.
Funder
National Natural Science Foundation of China
National Key Research and Development Program of China
Fundamental Research Funds for the Central Universities
Subject
General Chemistry,Catalysis
Cited by
13 articles.
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