title: TKD peptide as a ligand targeting drug delivery systems to memHsp70-positive breast cancer.
abstract: Breast cancer has been considered as a serious threat to females' life. Active targeting drug delivery is a potential strategy in cancer therapy, which however is hindered by the targeting efficiency. Herein, a 14-mer peptide (TKD) derived from the oligomerization domain of membrane heat-shock protein 70 (memHsp70), for the first time, was exploited as a tumor-targeting ligand to modify polymeric micelles. NMR results demonstrated the successful synthesis of TKD-PEG-PLGA polymer. No difference was observed in the drug release between TKD-modified doxorubicin (DOX)-loaded micelles (TKD-D-M) and unmodified counterparts. The modification of TKD mediated apparently higher cellular uptake within memHsp70-positive MCF-7 cells, compared to normal MCF-10A cells. Excessive TKD pretreatment significantly inhibited the cellular uptake of TKD-D-M, indicating the receptor-mediated mechanism. Enhanced accumulation of TKD-D-M within the tumor of MCF-7 bearing mice further demonstrated the targeting ability of TKD in vivo. CCK-8 assay showed that the modification of TKD significantly increase the anti-proliferation effect against MCF-7 cells. The findings demonstrated that TKD peptide is a potential ligand which can target drug delivery systems to memHsp70-positive breast cancer.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, 826 Zhangheng Road, Shanghai 201203, China; School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Meng
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Chengyi
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Min
authors.initials: M
authors.lastname: Qian
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Yufan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
authors.forename: Xueying
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, 826 Zhangheng Road, Shanghai 201203, China. Electronic address: rqhuang@fudan.edu.cn.
authors.forename: Rongqin
authors.initials: R
authors.lastname: Huang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011091:Polyesters / Q000008:administration & dosage / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D000970:Antineoplastic Agents; D018840:HSP70 Heat-Shock Proteins; D008024:Ligands; D010446:Peptide Fragments; D011091:Polyesters; C000589473:polyethylene glycol-poly(lactide-co-glycolide); D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: Active targeting; Breast cancer; Micelles; TKD peptide; memHsp70