Molecular optical imaging probes for early diagnosis of drug-induced acute kidney injury

Drug-induced acute kidney injury (AKI) with a high morbidity and mortality is poorly diagnosed in hospitals and deficiently evaluated in drug discovery. Here, we report the development of molecular renal probes (MRPs) with high renal clearance efficiency for in vivo optical imaging of drug-induced A...

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Main Authors: Huang, Jiaguo, Li, Jingchao, Lyu, Yan, Miao, Qingqing, Pu, Kanyi
Other Authors: School of Chemical and Biomedical Engineering
Format: Journal Article
Language:English
Published: 2019
Subjects:
Online Access:https://hdl.handle.net/10356/82606
http://hdl.handle.net/10220/48884
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author Huang, Jiaguo
Li, Jingchao
Lyu, Yan
Miao, Qingqing
Pu, Kanyi
author2 School of Chemical and Biomedical Engineering
author_facet School of Chemical and Biomedical Engineering
Huang, Jiaguo
Li, Jingchao
Lyu, Yan
Miao, Qingqing
Pu, Kanyi
author_sort Huang, Jiaguo
collection NTU
description Drug-induced acute kidney injury (AKI) with a high morbidity and mortality is poorly diagnosed in hospitals and deficiently evaluated in drug discovery. Here, we report the development of molecular renal probes (MRPs) with high renal clearance efficiency for in vivo optical imaging of drug-induced AKI. MRPs specifically activate their near-infrared fluorescence or chemiluminescence signals towards the prodromal biomarkers of AKI including the superoxide anion, N-acetyl-β-D-glucosaminidase and caspase-3, enabling an example of longitudinal imaging of multiple molecular events in the kidneys of living mice. Importantly, they in situ report the sequential occurrence of oxidative stress, lysosomal damage and cellular apoptosis, which precedes clinical manifestation of AKI (decreased glomerular filtration). Such an active imaging mechanism allows MRPs to non-invasively detect the onset of cisplatin-induced AKI at least 36 h earlier than the existing imaging methods. MRPs can also act as exogenous tracers for optical urinalysis that outperforms typical clinical/preclinical assays, demonstrating their clinical promise for early diagnosis of AKI.
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spelling ntu-10356/826062023-12-29T06:47:44Z Molecular optical imaging probes for early diagnosis of drug-induced acute kidney injury Huang, Jiaguo Li, Jingchao Lyu, Yan Miao, Qingqing Pu, Kanyi School of Chemical and Biomedical Engineering Diagnostics DRNTU::Engineering::Chemical engineering Fluorescent Probes Drug-induced acute kidney injury (AKI) with a high morbidity and mortality is poorly diagnosed in hospitals and deficiently evaluated in drug discovery. Here, we report the development of molecular renal probes (MRPs) with high renal clearance efficiency for in vivo optical imaging of drug-induced AKI. MRPs specifically activate their near-infrared fluorescence or chemiluminescence signals towards the prodromal biomarkers of AKI including the superoxide anion, N-acetyl-β-D-glucosaminidase and caspase-3, enabling an example of longitudinal imaging of multiple molecular events in the kidneys of living mice. Importantly, they in situ report the sequential occurrence of oxidative stress, lysosomal damage and cellular apoptosis, which precedes clinical manifestation of AKI (decreased glomerular filtration). Such an active imaging mechanism allows MRPs to non-invasively detect the onset of cisplatin-induced AKI at least 36 h earlier than the existing imaging methods. MRPs can also act as exogenous tracers for optical urinalysis that outperforms typical clinical/preclinical assays, demonstrating their clinical promise for early diagnosis of AKI. MOE (Min. of Education, S’pore) Accepted version 2019-06-20T08:40:43Z 2019-12-06T14:58:51Z 2019-06-20T08:40:43Z 2019-12-06T14:58:51Z 2019 2019 Journal Article Huang, J., Li, J., Lyu, Y., Miao, Q., & Pu, K. Molecular optical imaging probes for early diagnosis of drug-induced acute kidney injury. Nature Materials. doi:10.1038/s41563-019-0378-4 1476-1122 https://hdl.handle.net/10356/82606 http://hdl.handle.net/10220/48884 10.1038/s41563-019-0378-4 213966 en Nature Materials © 2019 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. This paper was published in Nature Materials and is made available with permission of Macmillan Publishers Limited, part of Springer Nature. 39 p. application/pdf
spellingShingle Diagnostics
DRNTU::Engineering::Chemical engineering
Fluorescent Probes
Huang, Jiaguo
Li, Jingchao
Lyu, Yan
Miao, Qingqing
Pu, Kanyi
Molecular optical imaging probes for early diagnosis of drug-induced acute kidney injury
title Molecular optical imaging probes for early diagnosis of drug-induced acute kidney injury
title_full Molecular optical imaging probes for early diagnosis of drug-induced acute kidney injury
title_fullStr Molecular optical imaging probes for early diagnosis of drug-induced acute kidney injury
title_full_unstemmed Molecular optical imaging probes for early diagnosis of drug-induced acute kidney injury
title_short Molecular optical imaging probes for early diagnosis of drug-induced acute kidney injury
title_sort molecular optical imaging probes for early diagnosis of drug induced acute kidney injury
topic Diagnostics
DRNTU::Engineering::Chemical engineering
Fluorescent Probes
url https://hdl.handle.net/10356/82606
http://hdl.handle.net/10220/48884
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AT miaoqingqing molecularopticalimagingprobesforearlydiagnosisofdruginducedacutekidneyinjury
AT pukanyi molecularopticalimagingprobesforearlydiagnosisofdruginducedacutekidneyinjury