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

Title
Epidermal growth factor (EGF)-based activatable probe for predicting therapeutic outcome of an EGF-based doxorubicin prodrug
Authors
권익찬김광명류주희심만규김한영엄상훈양수아박주호성예진김은선
Issue Date
2020-12
Publisher
Journal of controlled release
Citation
VOL 328-236
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.
URI
http://pubs.kist.re.kr/handle/201004/72397
ISSN
0168-3659
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