Theranostics 2014; 4(11):1096-1111. doi:10.7150/thno.9423

Research Paper

Co-delivery of Doxorubicin and Bmi1 siRNA by Folate Receptor Targeted Liposomes Exhibits Enhanced Anti-Tumor Effects in vitro and in vivo

Tan Yang1, Bin Li1, Shibo Qi1, Yong Liu1, Yongkang Gai1, Peng Ye1, Guang Yang1, Wendian Zhang1, Peng Zhang2, Xingxing He3, Weijie Li4, Zhiping Zhang1, Guangya Xiang1✉, Chuanrui Xu1✉

1. School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China, 430030;
2. Department of Oncology of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology;
3. Department of Hepatology of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology;
4. Department of Pharmacy of Tongji Hospital; Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China, 430030.

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Citation:
Yang T, Li B, Qi S, Liu Y, Gai Y, Ye P, Yang G, Zhang W, Zhang P, He X, Li W, Zhang Z, Xiang G, Xu C. Co-delivery of Doxorubicin and Bmi1 siRNA by Folate Receptor Targeted Liposomes Exhibits Enhanced Anti-Tumor Effects in vitro and in vivo. Theranostics 2014; 4(11):1096-1111. doi:10.7150/thno.9423. Available from https://www.thno.org/v04p1096.htm

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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.

Keywords: liposome, Bmi1 siRNA, doxorubicin, folate receptor, tumor targeting.