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Review
. 2021 Aug 17:9:720291.
doi: 10.3389/fbioe.2021.720291. eCollection 2021.

DNA Functional Nanomaterials for Controlled Delivery of Nucleic Acid-Based Drugs

Affiliations
Review

DNA Functional Nanomaterials for Controlled Delivery of Nucleic Acid-Based Drugs

Zhaoyue Lv et al. Front Bioeng Biotechnol. .

Abstract

Nucleic acid-based drugs exhibited great potential in cancer therapeutics. However, the biological instability of nucleic acid-based drugs seriously hampered their clinical applications. Efficient in vivo delivery is the key to the clinical application of nucleic acid-based drugs. As a natural biological macromolecule, DNA has unique properties, such as excellent biocompatibility, molecular programmability, and precise assembly controllability. With the development of DNA nanotechnology, DNA nanomaterials have demonstrated significant advantages as delivery vectors of nucleic acid-based drugs by virtue of the inherent nucleic acid properties. In this study, the recent progress in the design of DNA-based nanomaterials for nucleic acid delivery is summarized. The DNA nanomaterials are categorized according to the components including pure DNA nanomaterials, DNA-inorganic hybrid nanomaterials, and DNA-organic hybrid nanomaterials. Representative applications of DNA nanomaterials in the controlled delivery of nucleic acid-based drugs are exemplified to show how DNA nanomaterials are rationally and exquisitely designed to address application issues in cancer therapy. At the end of this study, the challenges and future development of DNA nanomaterials are discussed.

Keywords: DNA assembly; DNA nanomaterials; DNA nanotechnology; drug delivery; nucleic acid-based drugs.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Schematic illustration of DNA functional nanomaterials for nucleic acid-based drugs delivery. DNA functional nanomaterials were developed into three major categories: pure DNA nanomaterials (marked with green), DNA-inorganic nanomaterials (marked with orange), and DNA-inorganic nanomaterials (marked with red). Images in pure DNA nanomaterials section (clockwise); Adapted with permission from Lee et al. (2012). Adapted with permission from Chen et al. (2015). Copyright 2015, American Chemical Society. Adapted with permission from Liu et al. (2018). Copyright 2018, Wiley-VCH. Images in DNA-inorganic nanomaterials section (clockwise); pure DNA nanomaterials (clockwise); Adapted with permission from Huo et al. (2019). Adapted with permission from Li M. et al. (2019). Copyright 2019, Wiley-VCH. Adapted with permission from Wang et al. (2021). Copyright 2021, Wiley-VCH. Images in DNA-organic nanomaterials section (clockwise); Adapted with permission from Ding et al. (2018). Copyright 2018, Wiley-VCH. Adapted with permission from Li et al. (2021). Copyright 2021, Nature Publishing Group. Adapted with permission fromLiu et al., 2019. Copyright 2019, American Chemical Society. Adapted with permission from Han et al. (2021a). Copyright 2021, Elsevier Publishing Group.
FIGURE 2
FIGURE 2
Pure DNA nanoassembly for nucleic acid-based drugs delivery. (A) DNA tetrahedron for _targeted in vivo siRNA delivery. Adapted with permission from ref. Lee et al. (2012). (B) DNA nanoribbons for siRNA delivery. Adapted with permission from ref. Chen et al. (2015). Copyright 2015, American Chemical Society. (C) DNA origami for synergistic RNAi-/chemotherapy. Adapted with permission from ref. Liu et al. (2018). Copyright 2018, Wiley-VCH.
FIGURE 3
FIGURE 3
DNA-inorganic nanoassembly for nucleic acid-based drugs delivery. (A) Gold-DNA nanoassembly for efficient gene silencing with controllable transformation. Adapted with permission from ref. Huo and Gan (2019). Copyright 2019, Science Publishing Group. (B) Engineering Multifunctional DNA hybrid nanospheres through coordination-driven self-assembly for CpG delivery. Adapted with permission from ref. Li M. et al. (2019). Copyright 2019, Wiley-VCH. (C) DNA nanoflower for multifunctional DNAzyme delivery. Adapted with permission from ref. Wang et al. (2021). Copyright 2021, Wiley-VCH.
FIGURE 4
FIGURE 4
DNA-polymer nanoassembly for efficient siRNA delivery. (A) Crosslinked nucleic acid nanogel for effective siRNA delivery. Adapted with permission from Ding et al. (2018a). Copyright 2018, Wiley-VCH. (B) Cascade hybridization of hairpin DNA in polymeric nanoframework for precise siRNA delivery (Li et al., 2021). Copyright 2021, Nature Publishing Group.
FIGURE 5
FIGURE 5
DNA-supermolecule nanoassembly for nucleic acid delivery. (A) Multifunctional nucleic acid nanostructures for sgRNA/Cas9/antisense delivery. Adapted with permission from ref. Liu et al. (2019). Copyright 2019, American Chemical Society. (B) Crosslinked nucleic acid nanogel for effective siRNA delivery. (B) Co-assembly of branched antisense and siRNA for combined gene silencing and tumor therapy. Adapted with permission from ref. Liu et al. (2021). Copyright 2020, Wiley-VCH.
FIGURE 6
FIGURE 6
Nanoassembly via TA mediated nucleic acid assembly. (A) DNA-polyphenol nanocomplex for efficient DNAzyme and antisense DNA delivery. Adapted with permission from ref. Han et al. (2021a). Copyright 2021, Elsevier Publishing Group. (B) Nucleic acid nanocomplex through TA mediating self-assembly for smart drug delivery and gene therapy. Adapted with permission from ref. Han et al. (2021b). Copyright 2021, Elsevier Publishing Group.

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