title: Design and biological activity of epidermal growth factor receptor-targeted peptide doxorubicin conjugate.
abstract: The nonspecific toxicity of anticancer drug doxorubicin (DOX) toward both tumor and normal cells can result in serious side effects, thereby limiting its clinical applications. In this wok, epidermal growth factor receptor (EGFR) antagonist peptide GE11 was introduced into DOX structure via a disulfide bond which can be cleaved by reduced glutathione (GSH). We have investigated the intracellular delivery and in vitro cytotoxicity of GE11-DOX conjugate and free DOX in high (SMMC-7721) and low (MCF-7) EGFR expressing cancer cell models. GE11-DOX accumulated at higher levels in SMMC-7721 cells than in MCF-7 cells, while the cellular uptake of free DOX was almost the same in both cells. Furthermore, pretreating with anti-EGFR monoclonal antibody reduced intracellular accumulation of GE11-DOX in SMMC-7721, indicating the involvement of EGFR pathway in the transport of conjugate. Our results suggest that GE11-DOX conjugate has the potential to be a therapeutic agent for treating EGFR overexpressing tumor.
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, No. 25/Ln2200, XieTu Rd, Shanghai 200032, China.
authors.forename: Mingliang
authors.initials: M
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, No. 25/Ln2200, XieTu Rd, Shanghai 200032, China.
authors.forename: Danbo
authors.initials: D
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, No. 25/Ln2200, XieTu Rd, Shanghai 200032, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, No. 25/Ln2200, XieTu Rd, Shanghai 200032, China.
authors.forename: Junping
authors.initials: J
authors.lastname: Ao
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, No. 25/Ln2200, XieTu Rd, Shanghai 200032, China.
authors.forename: Zonghai
authors.initials: Z
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, No. 25/Ln2200, XieTu Rd, Shanghai 200032, China.
authors.forename: Hongyang
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, No. 25/Ln2200, XieTu Rd, Shanghai 200032, China. Electronic address: vanbright@163.com.
authors.forename: Bizhi
authors.initials: B
authors.lastname: Shi
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000378:metabolism*; D004317:Doxorubicin / Q000008:administration & dosage / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Epidermal growth factor receptor; Peptide drug conjugate; Targeted drug delivery