Branched Antisense and siRNA Co‐Assembled Nanoplatform for Combined Gene Silencing and Tumor Therapy,Angewandte Chemie International Edition

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Branched Antisense and siRNA Co‐Assembled Nanoplatform for Combined Gene Silencing and Tumor Therapy
Angewandte Chemie International Edition ( IF 16.1 ) Pub Date : 2020-10-15 , DOI: 10.1002/anie.202011174
Jianbing Liu _{1,

2} , Xuehe Lu _{1,

3} , Tiantian Wu _{1,

2} , Xiaohui Wu _{1,

2} , Lin Han _{1,

3} , Baoquan Ding _{1,

2,

3}

Affiliation

Chemically modified DNA has been widely developed to fabricate various nucleic acid nanostructures for biomedical applications. Herein, we report a facile strategy for construction of branched antisense DNA and small interfering RNA (siRNA) co‐assembled nanoplatform for combined gene silencing in vitro and in vivo. In our design, the branched antisense can efficiently capture siRNA with 3′ overhangs through DNA–RNA hybridization. After being equipped with an active targeting group and an endosomal escape peptide by host–guest interaction, the tailored nucleic acid nanostructure functions efficiently as both delivery carrier and therapeutic cargo, which is released by endogenous RNase H digestion. The multifunctional nucleic acid nanosystem elicits an efficient inhibition of tumor growth based on the combined gene silencing of the tumor‐associated gene polo‐like kinase 1 (PLK1). This biocompatible nucleic acid nanoplatform presents a new strategy for the development of gene therapy.

中文翻译：

分支反义和siRNA共组装的纳米平台，可用于基因沉默和肿瘤治疗

化学修饰的DNA已经被广泛开发以制造用于生物医学应用的各种核酸纳米结构。在此，我们报道了一种简便的策略，可用于构建分支反义DNA和小干扰RNA（siRNA）共组装的纳米平台，以在体内和体外组合基因沉默。在我们的设计中，分支反义可通过DNA-RNA杂交有效捕获3'突出的siRNA。通过宿主-客体相互作用配备了一个有活性的靶向基团和一个内体逃逸肽后，特制的核酸纳米结构既可以作为递送载体，又可以作为治疗性货物，通过内源性RNase H消化释放出来。多功能核酸纳米系统基于肿瘤相关基因polo样激酶1（PLK1）的组合基因沉默，可有效抑制肿瘤生长。这种生物相容性核酸纳米平台为基因治疗的发展提出了新的策略。

更新日期：2020-10-15

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