Renal clearable polyfluorophore nanosensors for early diagnosis of cancer and allograft rejection

Optical nanoparticles are promising diagnostic tools; however, their shallow optical imaging depth and slow clearance from the body have impeded their use for in vivo disease detection. To address these limitations, we develop activatable polyfluorophore nanosensors with biomarker-triggered nanopart...

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Main Authors: Huang, Jiaguo, Chen, Xiaona, Jiang, Yuyan, Zhang, Chi, He, Shasha, Wang, Hangxiang, Pu, Kanyi
Other Authors: School of Chemical and Biomedical Engineering
Format: Journal Article
Language:English
Published: 2022
Subjects:
Online Access:https://hdl.handle.net/10356/162237
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author Huang, Jiaguo
Chen, Xiaona
Jiang, Yuyan
Zhang, Chi
He, Shasha
Wang, Hangxiang
Pu, Kanyi
author2 School of Chemical and Biomedical Engineering
author_facet School of Chemical and Biomedical Engineering
Huang, Jiaguo
Chen, Xiaona
Jiang, Yuyan
Zhang, Chi
He, Shasha
Wang, Hangxiang
Pu, Kanyi
author_sort Huang, Jiaguo
collection NTU
description Optical nanoparticles are promising diagnostic tools; however, their shallow optical imaging depth and slow clearance from the body have impeded their use for in vivo disease detection. To address these limitations, we develop activatable polyfluorophore nanosensors with biomarker-triggered nanoparticle-to-molecule pharmacokinetic conversion and near-infrared fluorogenic turn-on response. Activatable polyfluorophore nanosensors can accumulate at the disease site and react with disease-associated proteases to undergo in situ enzyme-catalysed depolymerization. This disease-specific interaction liberates renal-clearable fluorogenic fragments from activatable polyfluorophore nanosensors for non-invasive longitudinal urinalysis and outperforms the gold standard blood and urine assays, providing a level of sensitivity and specificity comparable to those of invasive biopsy and flow cytometry analysis. In rodent models, activatable polyfluorophore nanosensors enable ultrasensitive detection of tumours (1.6 mm diameter) and early diagnosis of acute liver allograft rejection. We anticipate that our modular nanosensor platform may be applied for early diagnosis of a range of diseases via a simple urine test.
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spelling ntu-10356/1622372022-10-11T01:02:33Z Renal clearable polyfluorophore nanosensors for early diagnosis of cancer and allograft rejection Huang, Jiaguo Chen, Xiaona Jiang, Yuyan Zhang, Chi He, Shasha Wang, Hangxiang Pu, Kanyi School of Chemical and Biomedical Engineering Engineering::Bioengineering Diagnostics Tools Near Infrared Optical nanoparticles are promising diagnostic tools; however, their shallow optical imaging depth and slow clearance from the body have impeded their use for in vivo disease detection. To address these limitations, we develop activatable polyfluorophore nanosensors with biomarker-triggered nanoparticle-to-molecule pharmacokinetic conversion and near-infrared fluorogenic turn-on response. Activatable polyfluorophore nanosensors can accumulate at the disease site and react with disease-associated proteases to undergo in situ enzyme-catalysed depolymerization. This disease-specific interaction liberates renal-clearable fluorogenic fragments from activatable polyfluorophore nanosensors for non-invasive longitudinal urinalysis and outperforms the gold standard blood and urine assays, providing a level of sensitivity and specificity comparable to those of invasive biopsy and flow cytometry analysis. In rodent models, activatable polyfluorophore nanosensors enable ultrasensitive detection of tumours (1.6 mm diameter) and early diagnosis of acute liver allograft rejection. We anticipate that our modular nanosensor platform may be applied for early diagnosis of a range of diseases via a simple urine test. Ministry of Education (MOE) K.P. thanks the Ministry of Education Singapore, Academic Research Fund Tier 1 (2019-T1-002-045 RG125/19 and RT05/20) and Academic Research Fund Tier 2 (MOE2018-T2-2-042 and MOE-T2EP30220-0010) for financial support. H.W. thanks the Zhejiang Provincial Natural Science Foundation of China (LR19H160002) and the National Natural Science Foundation of China (82073296 and 81773193) for financial support. 2022-10-11T01:02:33Z 2022-10-11T01:02:33Z 2022 Journal Article Huang, J., Chen, X., Jiang, Y., Zhang, C., He, S., Wang, H. & Pu, K. (2022). Renal clearable polyfluorophore nanosensors for early diagnosis of cancer and allograft rejection. Nature Materials, 21(5), 598-607. https://dx.doi.org/10.1038/s41563-022-01224-2 1476-1122 https://hdl.handle.net/10356/162237 10.1038/s41563-022-01224-2 35422505 2-s2.0-85128016438 5 21 598 607 en 2019-T1-002-045 RG125/19 RT05/20 MOE2018-T2-2-042 MOE-T2EP30220-0010 Nature Materials © 2022 The Author(s), under exclusive licence to Springer Nature Limited. All rights reserved.
spellingShingle Engineering::Bioengineering
Diagnostics Tools
Near Infrared
Huang, Jiaguo
Chen, Xiaona
Jiang, Yuyan
Zhang, Chi
He, Shasha
Wang, Hangxiang
Pu, Kanyi
Renal clearable polyfluorophore nanosensors for early diagnosis of cancer and allograft rejection
title Renal clearable polyfluorophore nanosensors for early diagnosis of cancer and allograft rejection
title_full Renal clearable polyfluorophore nanosensors for early diagnosis of cancer and allograft rejection
title_fullStr Renal clearable polyfluorophore nanosensors for early diagnosis of cancer and allograft rejection
title_full_unstemmed Renal clearable polyfluorophore nanosensors for early diagnosis of cancer and allograft rejection
title_short Renal clearable polyfluorophore nanosensors for early diagnosis of cancer and allograft rejection
title_sort renal clearable polyfluorophore nanosensors for early diagnosis of cancer and allograft rejection
topic Engineering::Bioengineering
Diagnostics Tools
Near Infrared
url https://hdl.handle.net/10356/162237
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AT zhangchi renalclearablepolyfluorophorenanosensorsforearlydiagnosisofcancerandallograftrejection
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