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WIREs Nanomed Nanobiotechnol
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Multimodules integrated functional DNA nanomaterials for intelligent drug delivery

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Abstract Deoxyribonucleic acid (DNA) has been an emerging building block to construct functional biomaterials. Due to their programmable sequences and rich responsiveness, DNA has attracted rising attention in the construction of intelligent nanomaterials with predicable nanostructure and adjustable functions, which has shown great potential in drug delivery. On the one hand, the DNA sequences with molecule recognition, responsiveness, and therapeutic efficacy can be easily integrated to the framework of DNA nanomaterials by sequence designing; on the other hand, the rich chemical groups on DNA molecules provide binding points for other functional units. In this review, we divided the functionalization modules in the construction of DNA nanomaterials into three types, including targeting modules, responsive modules, and therapeutic modules. Based on these modules, five DNA kinds of representative nanomaterials applied in drug delivery were introduced, including DNA nanogel, DNA origami, DNA framework, DNA nanoflower, and DNA hybrid nanosphere. Finally, we discussed the challenges in the transition of DNA materials to clinical applications. We expect that this review can help readers to obtain a deeper understanding of DNA materials, and further promote the development of these intelligent materials to real world's application. This article is categorized under: Biology‐Inspired Nanomaterials > Nucleic Acid‐Based Structures Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Functional DNA nanostructures. (a) Targeting modules: DNA aptamer and DNA‐conjugated targeting units. (b) Responsive modules: triplex‐DNA, G‐quadruplex, i‐motif, DNAzyme, ATP‐aptamer, and disulfide bond‐DNA strand. (c) Therapeutic modules: drug loading units and functional nucleic acid
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The applications of DNA nanoflower and DNA hybrid nanosphere. (a) DNA nanoflowers for targeted drug delivery (L. Q. Zhang, Wang, et al., 2019). (b) Copper–DNAzyme hybrid nanosphere to delivery DNAzyme and Cu2+ for biocatalytic tumor therapy (C. Z. Liu, Chen, et al., 2021)
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DNA origami and DNA framework utilized in drug delivery. (a) DNA origami‐based nanodevice to provoke a robust tumor‐specific immune response for cancer therapy (C. Z. Liu, Chen, et al., 2021). (b) DNA origami for controlled therapeutic drug delivery (S. P. Li et al., 2018). (c) DNA tetrahedron for targeted platinum drug delivery (Wu et al., 2019). (d) DNA icosahedron for precise delivery of platinum nanodrugs (Ma et al., 2018)
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DNA nanogels utilized in drug delivery. (a) Hybrid chain reaction‐based DNA nanogel for precise siRNA delivery (F. Li et al., 2021). (b) Branched DNA‐based nanogel for smart drug delivery and gene therapy (Han, Cui, Li, et al., 2021). (c) Crosslinked DNA nanogel for effective siRNA delivery and antitumor therapy (Ding et al., 2018)
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The therapeutic modules in DNA nanomaterials. (a) DNA nanotrain delivered doxorubicin selectively to liver cancer cells (L. L. Zhang, Abdullah, et al., 2019). (b) DNA nanocarrier co‐loaded with antisense oligodeoxynucleotide for gene therapy (Wu et al., 2020). (c) a tubular DNA nanodevice as siRNA delivery vehicle for cancer therapy (Z. R. Wang, Song, et al., 2021)
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The responsive modules in DNA nanomaterials. (a) Triplex DNA‐based nanoswitch for pH‐sensitive drug release (X. X. Chen et al., 2019). (b) DNA‐Au nanomachine equipped with i‐motif and G‐Quadruplex for pH‐sensitive drug release (Park et al., 2018). (c) DNAzyme‐based nanosponge for pH‐sensitive drug release (H. M. Wang, Chen, et al., 2019). (d) ATP‐responsive DNA–graphene hybrid nanoaggregates for anticancer drug delivery (Mo et al., 2015)
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The targeting modules in DNA nanomaterials. (a) Aptamer‐tethered DNA nanodevice (aptND) for targeting to cell surfaces by in‐situ self‐assembly (G. Z. Zhu et al., 2013). (b) DNA cages modified by biotin as a cancer targeted probe (Huang et al., 2016). (c) DNA nanoclews hybridized with folic acid‐labeled ssDNA to achieve tumor‐targeting delivery (Sun et al., 2014). (d) A DNA tetrahedron labeled with cetuximab specifically targeting to epidermal growth factor receptor (Setyawati et al., 2016)
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Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures

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