Epidermal growth factor (EGF)-based activatable probe for predicting therapeutic outcome of an EGF-based doxorubicin prodrug

Han Young Kim, Sang Hoon Um, Yejin Sung, Man Kyu Shim, Suah Yang, Jooho Park, Eun Sun Kim, Kwangmeyung Kim, Ick Chan Kwon, Ju Hee Ryu

Research output: Contribution to journalArticle

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 fluorescence-activatable 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 EGF-prodrug 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.

Original languageEnglish
Pages (from-to)222-236
Number of pages15
JournalJournal of Controlled Release
Volume328
DOIs
Publication statusPublished - 2020 Dec 10

Keywords

  • Activatable probe
  • Colorectal cancer
  • Doxorubicin prodrug
  • Epidermal growth factor
  • Lysosomal enzyme

ASJC Scopus subject areas

  • Pharmaceutical Science

Fingerprint Dive into the research topics of 'Epidermal growth factor (EGF)-based activatable probe for predicting therapeutic outcome of an EGF-based doxorubicin prodrug'. Together they form a unique fingerprint.

  • Cite this