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

Research output: Contribution to journalArticlepeer-review

94 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 languageEnglish
Pages (from-to)130-140
Number of pages11
JournalBiomaterials
Volume122
DOIs
StatePublished - 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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