Static DNA Nanostructures For Cancer Theranostics: Recent Progress In Design And Applications

Abstract

Among the various nano/biomaterials used in cancer treatment, the beauty and benefits of DNA nanocomposites are outstanding. The specificity and programmability of the base pairing of DNA strands, together with their ability to conjugate with different types of functionalities have realized unsurpassed potential for the production of two- and three-dimensional nano-sized structures in any shape, size, surface chemistry and functionality. This review aims to provide an insight into the diversity of static DNA nanodevices, including DNA origami, DNA polyhedra, DNA origami arrays and bioreactors, DNA nanoswitch, DNA nanoflower, hydrogel and dendrimer as young but promising platforms for cancer theranostics. The utility and potential of the individual formats in biomedical science and especially in cancer therapy will be discussed.

Keywords: biosensing; cancer treatment; static DNA nanostructures.

Figure 1

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Figure 2

DON for targeted drug delivery. (A) Multiple-armed tetrahedral DNA nanostructure (TDNs) for dual-modality in vivo imaging and targeted cancer therapy. Adapted with permission from Jiang D, Sun Y, Li J, et al. Multiple-armed tetrahedral DNA nanostructures for tumor-targeting, dual-modality in vivo imaging. ACS Appl Mater Interfaces. 2016;8(7):4378–4384. doi:10.1021/ acsami.5b10792. Copyright (2016) American Chemical Society. (B) Triangle-shaped DNA origami affords optimum drug internalization for cancer chemotherapy. Adapted with permission from Zhang Q, Jiang Q, Li N, et al. DNA origami as an in vivo drug delivery vehicle for cancer therapy. ACS Nano. 2014;8(7):6633– 6643. doi:10.1021/nn502058j. Copyright (2014) American Chemical Society. (C) DON with a different degree of twist and relaxation achieves tunable drug release kinetics. Adapted with approval from Zhao YX, Shaw A, Zeng X, Benson E, Nystrom AM, Hogberg B. DNA origami delivery system for cancer therapy with tunable release properties. ACS Nano. 2012;6(10):8684–8691. doi:10.1021/nn3022662. Copyright ACS, https://pubs.acs.org/doi/abs/10.1021%2Fnn3022662. Further permissions related to the material excerpted should be directed to ACS.

Figure 3

DNA nanocage. (A) Inorganic nanoparticle inside the DNA cage as a hybrid drug delivery system. Reprinted with permission from Zhang C, Li X, Tian C, et al. DNA nanocages swallow gold nanoparticles (AuNPs) to form AuNP@DNA cage core-shell structures. ACS Nano. 2014;8(2):1130–1135. doi:10.1021/nn406039p. Copyright (2014) American Chemical Society. (B) Single protein encapsulated in rigid DNA tetrahedron nanocage. Reprinted with permission from Erben CM, Goodman RP, Turberfield AJ. Single-molecule protein encapsulation in a rigid DNA cage. Angew Chem Int Ed Engl. 2006;45(44):7414–7417. doi:10.1002/anie.200603392. John Wiley and Sons. (C) Doxorubicin-loaded tumor-penetrating peptide-modified DNA tetrahedron. Reprinted with permission from Xia Z, Wang P, Liu X, et al. Tumor-penetrating peptide-modified DNA tetrahedron for targeting drug delivery. Biochemistry. 2016;55 (9):1326–1331. doi:10.1021/acs.biochem.5b01181. Copyright (2016) American Chemical Society. (D) DNA nanosuitcases for encapsulation and conditional release of siRNA. Reprinted with permission from Bujold KE, Hsu JCC, Sleiman HF, Optimized DNA. “Nanosuitcases” for encapsulation and conditional release of siRNA. J Am Chem Soc. 2016;138(42):14030–14038. doi:10.1021/jacs.6b08369. Copyright (2016) American Chemical Society. (E) DNA tetrahedron structured probe (TSP) for protein biosensing. Adapted with permission from Pei H, Lu N, Wen Y, et al. A DNA nanostructure-based biomolecular probe carrier platform for electrochemical biosensing. Adv Mater. 2010;22(42):4754–4758. doi:10.1002/adma.201002767. John Wiley and Sons.

Figure 4

DNA origami arrays and bioreactors. (A) multi-protein decoration of DNA origami structures (arrays) resembling a human face. Adapted with permission from Sacca B, Meyer R, Erkelenz M, et al. Orthogonal protein decoration of DNA origami. Angew Chem Int Ed Engl. 2010;49(49):9378–9383. doi:10.1002/anie.201005931. John Wiley and Sons. (B) Assembly steps for the 2D nanocomponent arrays. Adapted with permission from Pinto YY, Le JD, Seeman NC, Musier-Forsyth K, Taton TA, Kiehl RA. Sequence-encoded self-assembly of multiple-nanocomponent arrays by 2D DNA scaffolding. Nano Lett. 2005;5(12):2399–2402. doi:10.1021/nl0515495. Copyright (2005) American Chemical Society. (C) 2D streptavidin nanoarrays on rectangular DNA origami surface. Adapted with permission from Kuzuya A, Kimura M, Numajiri K, et al. Precisely programmed and robust 2D streptavidin nanoarrays by using periodical nanometer-scale wells embedded in DNA origami assembly. Chembiochem. 2009;10(11):1811–1815. doi:10.1002/cbic.200900229. John Wiley and Sons.

Figure 5

DNA nanoflower preparation and its biomedical applications. (A) miRNA initiated the growth and blooming of DNA nanoflower in nanochannel. Adapted with permission from Shi L, Mu C, Gao T, et al. DNA nanoflower blooms in nanochannels: a new strategy for miRNA detection. Chem Commun. 2018;54(81):11391–11394. doi:10.1039/c8cc05690k. Permission conveyed through Copyright Clearance Center, Inc. (B) DNA nanoflowers for multiplexed cellular imaging and traceable targeted drug delivery. Adapted from Hu R, Zhang X, Zhao Z, et al. DNA nanoflowers for multiplexed cellular imaging and traceable targeted drug delivery. Angew Chem Int Ed Engl. 2014;53(23):5821–5826. doi:10.1002/anie.201400323. John Wiley and Sons. (C) RCR-based assembly of NFs loaded with chemotherapeutics for targeted drug delivery. Reprinted by permission from Springer Nature: Lv Y, Hu R, Zhu G, et al. Preparation and biomedical applications of programmable and multifunctional DNA nanoflowers. Nat Protoc. 2015;10(10):1508–1524. doi:10.1038/nprot.2015.078. Copyright (2015). (D) Synergistic immunotherapy of cancer by DNA-RNA microflowers (iDR-MFs) loaded with tumor neoantigens. Adapted with permission from Zhu G, Mei L, Vishwasrao HD, et al. Intertwining DNA-RNA nanocapsules loaded with tumor neoantigens as synergistic nano-vaccines for cancer immunotherapy. Nat Commun. 2017;8(1):1482. doi:10.1038/s41467-017-01386.

Figure 6

Design and application of DNA dendrimer in biomedicine. (A) DNA dendrimer–streptavidin for efficient signal amplification for biosensing. Adapted with permission from Zhao Y, Hu S, Wang H, et al. DNA dendrimer–streptavidin nanocomplex: an efficient signal amplifier for construction of biosensing platforms. Anal Chem. 2017;89(12):6907–6914. doi:10.1021/acs. analchem.7b01551. Copyright (2017) American Chemical Society. (B) Multifunctional DNA dendrimers. Adapted with permission from Qu Y, Yang J, Zhan P, et al. Self-assembled DNA dendrimer nanoparticle for efficient delivery of immunostimulatory CpG motifs. ACS Appl Mater Interfaces. 2017;9(24):20324–20329. doi:10.1021/acsami.7b05890. Copyright (2017) American Chemical Society.

Figure 7

Design and application of DNA hydrogels in biomedicine. (A) Schematic representation of the photo-responsive properties of DNA hydrogels for on-demand cargo release of the payloads. Adapted with permission from Kang H, Liu H, Zhang X, et al. Photoresponsive DNA-cross-linked hydrogels for controllable release and cancer therapy. Langmuir. 2011;27(1):399–408. doi:10.1021/la1037553. Copyright (2011) American Chemical Society. (B) Apatmer (EpCAM) binding-mediated catalysis of HCR control gel-sol state of ATP-responsive DNA hydrogel, resulting in cloaking (gel state) and releasing (sol state) of circulating tumor cells. Adapted with permission from Song P, Ye D, Zuo X, et al. DNA hydrogel with aptamer-toeholdbased recognition, cloaking, and decloaking of circulating tumor cells for live cell analysis. Nano Lett. 2017;17(9):5193–5198. doi:10.1021/acs.nanolett.7b01006. Copyright (2017) American Chemical Society. (C) Self-assembly of aptamer-based nanohydrogel using Y-shaped building blocks for targeted cancer gene therapy. Adapted with permission from Li J, Zheng C, Cansiz S, et al. Self-assembly of DNA nanohydrogels with controllable size and stimuli-responsive property for targeted gene regulation therapy. J Am Chem Soc. 2015;137(4):1412–1415. doi:10.1021/ja512293f. Copyright ACS, https://pubs.acs.org/doi/abs/10.1021%2Fnn3022662. Further permissions related to the material excerpted should be directed to ACS.

Figure 8

DNA nanoswitch systems as cancer theranostics. (A) Azobenzene-integrated photo controlled drug release from DNA/mesoporous silica. Adapted with permission from YuanQ, ZhangY,Chen T, et al. Photon-manipulated drug release from a mesoporous nanocontainer controlled by azobenzene-modified nucleic acid. ACS Nano. 2012;6(7):6337–6344. doi:10.1021/nn3018365. Copyright (2012) American Chemical Society. (B) Redox stimuli-responsive drug release of the PMAA nanohydrogels. Adapted with permission from Pan YJ, Chen YY, Wang DR, et al. Redox/pH dual stimuli-responsive biodegradable nanohydrogels with varying responses to dithiothreitol and glutathione for controlled drug release. Biomaterials. 2012;33(27):6570–6579. doi:10.1016/j.biomaterials.2012.05.062, copyright (2012), with permission from Elsevier (C) Aptamer-based DNA nanoswitch for controlled drug release. Adapted with approval of Mo R, Jiang T, Sun W, Gu Z. ATP-responsive DNA-graphene hybrid nanoaggregates for anticancer drug delivery. Biomaterials. 2015;50:67–74. doi:10.1016/j.biomaterials.2015.01.053, copyright (2015) with permission from Elsevier.