Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 60, Issue 4, Pages 1853-1860Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202011174
Keywords
cancer therapy; drug delivery; gene therapy; nucleic acid nanostructure; self-assembly
Categories
Funding
- National Natural Science Foundation of China [21708004, 21721002]
- National Basic Research Program of China [2016YFA0201601, 2018YFA0208900]
- Beijing Municipal Science & Technology Commission [Z191100004819008]
- Strategic Priority Research Program of Chinese Academy of Sciences [XDB36000000]
- Key Research Program of Frontier Sciences, CAS [QYZDB-SSW-SLH029]
- CAS Interdisciplinary Innovation Team
- K. C. Wong Education Foundation [GJTD-2018-03]
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This study presents a novel strategy for constructing a nanoplatform that combines branched antisense DNA and siRNA for gene silencing. The multifunctional nucleic acid nanosystem efficiently inhibits tumor growth by targeting the tumor-associated gene PLK1 through combined gene silencing.
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.
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