Co-delivery of doxorubicin and Bmi1 siRNA by folate receptor targeted liposomes exhibits enhanced anti-tumor effects in vitro and in vivo.
Co-delivery of doxorubicin and Bmi1 siRNA by folate receptor targeted liposomes exhibits enhanced anti-tumor effects in vitro and in vivo.
复制标题
通过叶酸受体靶向脂质体共同递送阿霉素和 Bmi 1 siRNA，在体外和体内表现出增强的抗肿瘤作用
作者：
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
Bmi 1基因在多种人类肿瘤中存在过表达，并已被证明是基因治疗的潜在靶点。然而，靶向Bmi 1基因的siRNA治疗方法局限于有限的递送、低生物利用度，因此相对降低了疗效。为了克服这些障碍，我们开发了叶酸受体靶向的叶酸-多柔比星/Bmi 1 siRNA脂质体（FA-DOX/siRNA-L）共递送系统。通过叶酸阿霉素脂质体（FA-DOX-L）与Bmi 1 siRNA的静电相互作用制备FA-DOX/siRNA-L。体内外研究表明，FA-DOX/siRNA-L通过联合Bmi 1 siRNA和阿霉素（DOX）的作用抑制肿瘤生长。通过FA-DOX/siRNA-L共递送Bmi 1 siRNA和DOX显示出比单独递送DOX或Bmi 1 siRNA显著更高的功效。Real-time PCR和western blot分析表明FA-DOX/siRNA-L沉默了Bmi 1基因的表达。此外，siRNA和DOX在肿瘤细胞中的较高积累表明叶酸配体具有肿瘤靶向作用。这些结果表明，Bmi 1是基于siRNA的癌症治疗的有效治疗靶标，其可以通过靶向脂质体共递送DOX来进一步改善。
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.
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影响因子：
13.3
作者：
Chen, Alex M.;Zhang, Min;Wei, Dongguang;Stueber, Dirk;Taratula, Oleh;Minko, Tamara;He, Huixin
通讯作者：
He, Huixin
影响因子：
17.1
作者：
Meng H;Liong M;Xia T;Li Z;Ji Z;Zink JI;Nel AE
通讯作者：
Nel AE
影响因子：
2.4
作者：
Perez, AT;Domenech, GH;Vogel, CL
通讯作者：
Vogel, CL
影响因子：
2.7
作者：
Henne, Walter A.;Doorneweerd, Derek D.;Low, Philip S.
通讯作者：
Low, Philip S.
影响因子：
4.7
作者：
Gabizon, A;Horowitz, AT;Zalipsky, S
通讯作者：
Zalipsky, S