Programmably tiling rigidified DNA brick on gold nanoparticle as multi-functional shell for cancer-targeted delivery of siRNAs

Chang Xue, Shuyao Hu, Zhi-Hua Gao, Lei Wang, Meng-Xue Luo, Xin Yu, Bi-Fei Li, Zhifa Shen and Zai-Sheng Wu ()
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Chang Xue: Fuzhou University
Shuyao Hu: Fuzhou University
Zhi-Hua Gao: Institute of Functional Nucleic Acids and Personalized Cancer Theranostics, Wenzhou Medical University
Lei Wang: Hunan Agricultural University
Meng-Xue Luo: Fuzhou University
Xin Yu: Fuzhou University
Bi-Fei Li: Fuzhou University
Zhifa Shen: Institute of Functional Nucleic Acids and Personalized Cancer Theranostics, Wenzhou Medical University
Zai-Sheng Wu: Fuzhou University

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract Small interfering RNA (siRNA) is an effective therapeutic to regulate the expression of target genes in vitro and in vivo. Constructing a siRNA delivery system with high serum stability, especially responsive to endogenous stimuli, remains technically challenging. Herein we develop anti-degradation Y-shaped backbone-rigidified triangular DNA bricks with sticky ends (sticky-YTDBs) and tile them onto a siRNA-packaged gold nanoparticle in a programmed fashion, forming a multi-functional three-dimensional (3D) DNA shell. After aptamers are arranged on the exterior surface, a biocompatible siRNA-encapsulated core/shell nanoparticle, siRNA/Ap-CS, is achieved. SiRNAs are internally encapsulated in a 3D DNA shell and are thus protected from enzymatic degradation by the outermost layer of YTDB. The siRNAs can be released by endogenous miRNA and execute gene silencing within tumor cells, causing cell apoptosis higher than Lipo3000/siRNA formulation. In vivo treatment shows that tumor growth is completely (100%) inhibited, demonstrating unique opportunities for next-generation anticancer-drug carriers for targeted cancer therapies.

Date: 2021
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DOI: 10.1038/s41467-021-23250-5

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