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 2024-01-19T16:01:06Z 2024-01-19T16:01:06Z 2021-09-02 2020-12-10 0168-3659 https://pubs.kist.re.kr/handle/201004/117689 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. English ELSEVIER FACTOR RECEPTOR IN-VIVO COLORECTAL-CANCER CATHEPSIN-B DEGRADATION CELLS ACIDIFICATION CHEMOTHERAPY EXPRESSION CONJUGATE Epidermal growth factor (EGF)-based activatable probe for predicting therapeutic outcome of an EGF-based doxorubicin prodrug Article 10.1016/j.jconrel.2020.08.046 1 JOURNAL OF CONTROLLED RELEASE, v.328, pp.222 - 236 JOURNAL OF CONTROLLED RELEASE 328 222 236 scie scopus 000600791600016 2-s2.0-85090248020 Chemistry, Multidisciplinary Pharmacology & Pharmacy Chemistry Pharmacology & Pharmacy Article FACTOR RECEPTOR IN-VIVO COLORECTAL-CANCER CATHEPSIN-B DEGRADATION CELLS ACIDIFICATION CHEMOTHERAPY EXPRESSION CONJUGATE Epidermal growth factor Lysosomal enzyme Activatable probe Doxorubicin prodrug Colorectal cancer