In vivo near-infrared imaging and phototherapy of tumors using a cathepsin B-activated fluorescent probe

Xiaoqiang Chen; Dayoung Lee; Sungsook Yu; Gyoungmi Kim; Songyi Lee; Yejin Cho; Haengdueng Jeong; Ki Taek Nam; Juyoung Yoon

doi:10.1016/j.biomaterials.2017.01.020

In vivo near-infrared imaging and phototherapy of tumors using a cathepsin B-activated fluorescent probe

Xiaoqiang Chen, Dayoung Lee, Sungsook Yu, Gyoungmi Kim, Songyi Lee, Yejin Cho, Haengdueng Jeong, Ki Taek Nam, Juyoung Yoon

Chemistry & Nanoscience

Research output: Contribution to journal › Article › peer-review

86 Scopus citations

Abstract

The development of multifunctional reagents for simultaneous specific near-infrared (NIR) imaging and phototherapy of tumors is of great significance. This work describes the design of a cathepsin B-activated fluorescent probe (CyA-P-CyB) and its applications as an NIR imaging probe for tumor cells and as a phototherapy reagent for tumors. In vitro experiments demonstrated that CyA-P-CyB was activated via the cleavage of a peptide linker by cathepsin B in tumor cells to produce fluorescence in the NIR region based on a FRET mechanism. MTT assays showed that the phototoxicity of CyA-P-CyB toward cells depended on the activity of cathepsin B, and the probe exhibited specific phototoxicity toward tumor cells. CyA-P-CyB was also successfully applied to the in vivo imaging and phototherapy of tumors. Histological analysis indicated that CyA-P-CyB had no cytotoxic effects on seven mouse tissues (lung, liver, heart, kidney, pancreas, spleen and brain) after the CyA-P-CyB treatment and laser irradiation.

Original language	English
Pages (from-to)	130-140
Number of pages	11
Journal	Biomaterials
Volume	122
DOIs	https://doi.org/10.1016/j.biomaterials.2017.01.020
State	Published - 1 Apr 2017

Bibliographical note

Funding Information:
This research was supported financially by grants from the National Creative Research Initiative Program (2012R1A3A2048814). It was also supported by the Korea Mouse Phenotyping Center (2016M3A9D5A01952416), and the Brain Korea 21 PLUS Project for Medical Science, Yonsei University, the Bio and Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF-2013M3A9D5072551). X. Chen acknowledges funding from the National Natural Science Foundation of China (21376117), the Jiangsu Natural Science Funds for Distinguished Young Scholars (BK20140043), and the Natural Science Foundation of Jiangsu Higher Education Institutions of China (14KJA150005).

Publisher Copyright:
© 2017 Elsevier Ltd

Keywords

Enzyme-activated fluorescence
Multiple functional probe
NIR bioimaging
Specific phototherapy

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10.1016/j.biomaterials.2017.01.020

Cite this

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title = "In vivo near-infrared imaging and phototherapy of tumors using a cathepsin B-activated fluorescent probe",

abstract = "The development of multifunctional reagents for simultaneous specific near-infrared (NIR) imaging and phototherapy of tumors is of great significance. This work describes the design of a cathepsin B-activated fluorescent probe (CyA-P-CyB) and its applications as an NIR imaging probe for tumor cells and as a phototherapy reagent for tumors. In vitro experiments demonstrated that CyA-P-CyB was activated via the cleavage of a peptide linker by cathepsin B in tumor cells to produce fluorescence in the NIR region based on a FRET mechanism. MTT assays showed that the phototoxicity of CyA-P-CyB toward cells depended on the activity of cathepsin B, and the probe exhibited specific phototoxicity toward tumor cells. CyA-P-CyB was also successfully applied to the in vivo imaging and phototherapy of tumors. Histological analysis indicated that CyA-P-CyB had no cytotoxic effects on seven mouse tissues (lung, liver, heart, kidney, pancreas, spleen and brain) after the CyA-P-CyB treatment and laser irradiation.",

keywords = "Enzyme-activated fluorescence, Multiple functional probe, NIR bioimaging, Specific phototherapy",

author = "Xiaoqiang Chen and Dayoung Lee and Sungsook Yu and Gyoungmi Kim and Songyi Lee and Yejin Cho and Haengdueng Jeong and Nam, {Ki Taek} and Juyoung Yoon",

note = "Funding Information: This research was supported financially by grants from the National Creative Research Initiative Program (2012R1A3A2048814). It was also supported by the Korea Mouse Phenotyping Center (2016M3A9D5A01952416), and the Brain Korea 21 PLUS Project for Medical Science, Yonsei University, the Bio and Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF-2013M3A9D5072551). X. Chen acknowledges funding from the National Natural Science Foundation of China (21376117), the Jiangsu Natural Science Funds for Distinguished Young Scholars (BK20140043), and the Natural Science Foundation of Jiangsu Higher Education Institutions of China (14KJA150005). Publisher Copyright: {\textcopyright} 2017 Elsevier Ltd",

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AU - Chen, Xiaoqiang

AU - Lee, Dayoung

AU - Yu, Sungsook

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AU - Lee, Songyi

AU - Cho, Yejin

AU - Jeong, Haengdueng

AU - Nam, Ki Taek

AU - Yoon, Juyoung

N1 - Funding Information: This research was supported financially by grants from the National Creative Research Initiative Program (2012R1A3A2048814). It was also supported by the Korea Mouse Phenotyping Center (2016M3A9D5A01952416), and the Brain Korea 21 PLUS Project for Medical Science, Yonsei University, the Bio and Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF-2013M3A9D5072551). X. Chen acknowledges funding from the National Natural Science Foundation of China (21376117), the Jiangsu Natural Science Funds for Distinguished Young Scholars (BK20140043), and the Natural Science Foundation of Jiangsu Higher Education Institutions of China (14KJA150005). Publisher Copyright: © 2017 Elsevier Ltd

PY - 2017/4/1

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N2 - The development of multifunctional reagents for simultaneous specific near-infrared (NIR) imaging and phototherapy of tumors is of great significance. This work describes the design of a cathepsin B-activated fluorescent probe (CyA-P-CyB) and its applications as an NIR imaging probe for tumor cells and as a phototherapy reagent for tumors. In vitro experiments demonstrated that CyA-P-CyB was activated via the cleavage of a peptide linker by cathepsin B in tumor cells to produce fluorescence in the NIR region based on a FRET mechanism. MTT assays showed that the phototoxicity of CyA-P-CyB toward cells depended on the activity of cathepsin B, and the probe exhibited specific phototoxicity toward tumor cells. CyA-P-CyB was also successfully applied to the in vivo imaging and phototherapy of tumors. Histological analysis indicated that CyA-P-CyB had no cytotoxic effects on seven mouse tissues (lung, liver, heart, kidney, pancreas, spleen and brain) after the CyA-P-CyB treatment and laser irradiation.

AB - The development of multifunctional reagents for simultaneous specific near-infrared (NIR) imaging and phototherapy of tumors is of great significance. This work describes the design of a cathepsin B-activated fluorescent probe (CyA-P-CyB) and its applications as an NIR imaging probe for tumor cells and as a phototherapy reagent for tumors. In vitro experiments demonstrated that CyA-P-CyB was activated via the cleavage of a peptide linker by cathepsin B in tumor cells to produce fluorescence in the NIR region based on a FRET mechanism. MTT assays showed that the phototoxicity of CyA-P-CyB toward cells depended on the activity of cathepsin B, and the probe exhibited specific phototoxicity toward tumor cells. CyA-P-CyB was also successfully applied to the in vivo imaging and phototherapy of tumors. Histological analysis indicated that CyA-P-CyB had no cytotoxic effects on seven mouse tissues (lung, liver, heart, kidney, pancreas, spleen and brain) after the CyA-P-CyB treatment and laser irradiation.

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JO - Biomaterials

JF - Biomaterials

ER -

In vivo near-infrared imaging and phototherapy of tumors using a cathepsin B-activated fluorescent probe

Abstract

Bibliographical note

Keywords

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