Epidermal growth factor (EGF)-based activatable probe for predicting therapeutic outcome of an EGF-based doxorubicin prodrug
- Authors
- Kim, Han Young; Um, Sang Hoon; Sung, Yejin; Shim, Man Kyu; Yang, Suah; Park, Jooho; Kim, Eun Sun; Kim, Kwangmeyung; Kwon, Ick Chan; Ryu, Ju Hee
- Issue Date
- 10-12월-2020
- Publisher
- ELSEVIER
- Keywords
- Epidermal growth factor; Lysosomal enzyme; Activatable probe; Doxorubicin prodrug; Colorectal cancer
- Citation
- JOURNAL OF CONTROLLED RELEASE, v.328, pp.222 - 236
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF CONTROLLED RELEASE
- Volume
- 328
- Start Page
- 222
- End Page
- 236
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/50819
- DOI
- 10.1016/j.jconrel.2020.08.046
- ISSN
- 0168-3659
- Abstract
- One of the most promising approaches for the treatment of colorectal cancer is targeting epidermal growth factor receptor (EGFR). Comprehensive research has led to significant clinical outcomes using EGFR-targeted anticancer drugs; however, the response to these drugs still largely varies among individuals. The current diagnostic platform provides limited information that does not enable successful prediction of the anticancer performance of EGFR-targeted drugs. Here, we developed a EGFR-targeted activatable probe for predicting therapeutic efficacy of EGFR-targeted doxorubicin prodrug in colorectal cancer therapy. The EGF-conjugated fluorescenceactivatable probe (EGF-probe) and EGF-conjugated doxorubicin prodrug (EGF-prodrug) were both fabricated using peptide substrates that can be dissociated by lysosomal enzymes, and thus share an intracellular mechanism of action. We demonstrated that after EGFR-mediated endocytosis, lysosomal enzymes de-quench the fluorescence of EGF-probe and activate the cytotoxicity of EGF-prodrug. When evaluated in vivo, EGF-probe yielded an outstanding cancer-specific imaging ability with reduced background signals. EGF-prodrug also successfully targeted the tumor and promoted cancer cell death. We tested different colorectal cancer cell types to investigate the correlation between the fluorescence recovery efficiency of EGF-probe and the cytotoxicity of EGF-prodrug. Strong correlations were observed both in vitro and in vivo. The actions of EGF-probe and EGFprodrug were dependent on the inherent lysosomal activity of the cell type rather than its EGFR expression level. Our proposed approach using EGF-probe and EGF-prodrug may overcome the major drawback of the conventional theranostic platform and provide great opportunity for successful personalized cancer therapy.
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- Appears in
Collections - College of Medicine > Department of Medical Science > 1. Journal Articles
- Graduate School > KU-KIST Graduate School of Converging Science and Technology > 1. Journal Articles
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