title: Co-delivery of doxorubicin and Bmi1 siRNA by folate receptor targeted liposomes exhibits enhanced anti-tumor effects in vitro and in vivo.
abstract: Bmi1 gene overexpression is found in various human tumors and has been shown as a potential target for gene treatment. However, siRNA-based treatments targeting Bmi1 gene have been restricted to limited delivery, low bioavailability and hence relatively reduced efficacy. To overcome these barriers, we developed a folate receptor targeted co-delivery system folate-doxorubicin/Bmi1 siRNA liposome (FA-DOX/siRNA-L). The FA-DOX/siRNA-L was prepared through electrostatic interaction between folate doxorubicin liposome (FA-DOX-L) and Bmi1 siRNA. In vitro and in vivo studies showed that FA-DOX/siRNA-L inhibited tumor growth by combinatory role of Bmi1 siRNA and doxorubicin (DOX). Co-delivery of Bmi1 siRNA and DOX by FA-DOX/siRNA-L showed significantly higher efficacy than sole delivery of either DOX or Bmi1 siRNA. Real-time PCR and western blot analysis showed that FA-DOX/siRNA-L silenced the expression of Bmi1 gene. In addition, higher accumulation of the siRNA and DOX in tumor cells indicated that folate ligand displayed tumor targeting effect. These results suggest that Bmi1 is an effective therapeutic target for siRNA based cancer treatment that can be further improved by co-delivery of DOX through targeted liposomes.
authors.affiliation: 1. School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China, 430030;
authors.forename: Tan
authors.initials: T
authors.lastname: Yang
authors.affiliation: 1. School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China, 430030;
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: 1. School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China, 430030;
authors.forename: Shibo
authors.initials: S
authors.lastname: Qi
authors.affiliation: 1. School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China, 430030;
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: 1. School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China, 430030;
authors.forename: Yongkang
authors.initials: Y
authors.lastname: Gai
authors.affiliation: 1. School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China, 430030;
authors.forename: Peng
authors.initials: P
authors.lastname: Ye
authors.affiliation: 1. School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China, 430030;
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: 1. School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China, 430030;
authors.forename: Wendian
authors.initials: W
authors.lastname: Zhang
authors.affiliation: 2. Department of Oncology of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology;
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: 3. Department of Hepatology of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology;
authors.forename: Xingxing
authors.initials: X
authors.lastname: He
authors.affiliation: 4. Department of Pharmacy of Tongji Hospital; Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China, 430030.
authors.forename: Weijie
authors.initials: W
authors.lastname: Li
authors.affiliation: 1. School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China, 430030;
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: 1. School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China, 430030;
authors.forename: Guangya
authors.initials: G
authors.lastname: Xiang
authors.affiliation: 1. School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China, 430030;
authors.forename: Chuanrui
authors.initials: C
authors.lastname: Xu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000008:administration & dosage; D005260:Female; D058975:Folate Receptor 1 / Q000819:agonists*; D005492:Folic Acid / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D008081:Liposomes / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D063150:Polycomb Repressive Complex 1 / Q000037:antagonists & inhibitors*; D034741:RNA, Small Interfering / Q000493:pharmacokinetics*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C069077:BMI1 protein, human; D004337:Drug Carriers; D058975:Folate Receptor 1; D008081:Liposomes; D034741:RNA, Small Interfering; D004317:Doxorubicin; D005492:Folic Acid; D063150:Polycomb Repressive Complex 1
keywords: Bmi1 siRNA; doxorubicin; folate receptor; liposome; tumor targeting.