Targeted delivery of siRNA-generating DNA nanocassettes using multifunctional nanoparticles.
Targeted delivery of siRNA-generating DNA nanocassettes using multifunctional nanoparticles.
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DOI：
10.1002/smll.201201973
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发表时间：
2013-06-10
期刊：
影响因子：
13.3
通讯作者：
Yang, Lily
中科院分区：
文献类型：
--
作者：
Cho, Young-Seok;Lee, Gee Young;Sajja, Hari Krishna;Qian, Weiping;Cao, Zehong;He, Weiling;Karna, Prasanthi;Chen, Xiaoyuan;Mao, Hui;Wang, Y. Andrew;Yang, Lily
使用小干扰RNA（siRNA）的分子治疗在新疗法的开发中显示出希望。各种制剂已用于siRNA的体内递送。然而，短的双链RNA分子在血液中的稳定性和siRNA在全身给药后递送到靶器官或组织中的效率一直是限制siRNA在人类患者中应用的主要问题。在这项研究中，开发了多功能siRNA递送纳米颗粒，其将纳米颗粒的成像能力与表达DNA纳米囊的siRNA的尿激酶纤溶酶原激活物受体靶向递送结合联合收割机。该治疗诊断纳米颗粒平台由与靶向配体缀合的纳米颗粒和含有U6启动子和用于体内siRNA表达的shRNA基因的双链DNA纳米囊组成。在肿瘤细胞和动物肿瘤模型中证明了萤火虫荧光素酶siRNA纳米发生器的靶向递送和基因沉默效率。将表达生存素siRNA的纳米囊泡递送到肿瘤细胞中诱导凋亡性细胞死亡并使细胞对化疗药物敏感。在受体介导的内化之后，从缀合至单个纳米颗粒的多个纳米囊表达siRNA的能力应当增强siRNA介导的癌症疗法的治疗效果。
Molecular therapy using a small interfering RNA (siRNA) has shown promise in the development of novel therapeutics. Various formulations have been used for in vivo delivery of siRNAs. However, the stability of short double-stranded RNA molecules in the blood and efficiency of siRNA delivery into target organs or tissues following systemic administration have been the major issues that limit applications of siRNA in human patients. In this study, multifunctional siRNA delivery nanoparticles are developed that combine imaging capability of nanoparticles with urokinase plasminogen activator receptor-targeted delivery of siRNA expressing DNA nanocassettes. This theranostic nanoparticle platform consists of a nanoparticle conjugated with targeting ligands and double-stranded DNA nanocassettes containing a U6 promoter and a shRNA gene for in vivo siRNA expression. Targeted delivery and gene silencing efficiency of firefly luciferase siRNA nanogenerators are demonstrated in tumor cells and in animal tumor models. Delivery of survivin siRNA expressing nanocassettes into tumor cells induces apoptotic cell death and sensitizes cells to chemotherapy drugs. The ability of expression of siRNAs from multiple nanocassettes conjugated to a single nanoparticle following receptor-mediated internalization should enhance the therapeutic effect of the siRNA-mediated cancer therapy.
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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：
10.8
作者：
Hasan W;Chu K;Gullapalli A;Dunn SS;Enlow EM;Luft JC;Tian S;Napier ME;Pohlhaus PD;Rolland JP;DeSimone JM
通讯作者：
DeSimone JM
影响因子：
12.4
作者：
Abdelmawla, Sherine;Guo, Songchuan;Li, Qi-Xiang
通讯作者：
Li, Qi-Xiang
影响因子：
4.8
作者：
Dohi, T;Okada, K;Altieri, DC
通讯作者：
Altieri, DC
影响因子：
4.5
作者：
Castanotto, D;Li, HT;Rossi, JJ
通讯作者：
Rossi, JJ