Abstract
Nanopharmaceuticals are systems in which therapeutic drug delivery works at the nanoscale. Even though several such systems are developed, most of them possess significant drawbacks. Some noted drawbacks include immunogenicity, cytotoxicity, accessibility to the target tissue, in vivo stability, biocompatibility, and effort in synthesizing procedure composed of complicated chemical reactions or techniques. Therefore, studies concerned with the fabrication of nanostructures based on biomolecules gained wide interest. The unique characteristics of biomolecules like DNA enable them to self-assemble and develop into variable nanostructures having tremendous applications. In this review, we focus on nanostructures fabricated from DNA. Their biocompatibility, structural stability, and unique recognition sites make them most suitable building blocks for the development of smart nanostructures. The first DNA-based nanostructure was a stick cube with a motif-based design. Incorporation of materials like polymers, development of newer technique like DNA origami, and the possibility of further modifications in the developed structures enable its high utility. In this review, we discuss concepts and applications of DNA nanostructures, DNA–polymer assembly, DNA origami technique, and structural modifications of DNA nanostructures.
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References
Albert SK, Golla M, Thelu HV, Krishnan N, Varghese R (2017) A pH-responsive DNAsome from the self-assembly of DNA phenyleneethynylene hybrid amphiphile. Chemistry 23(35):8348–8352. https://doi.org/10.1002/chem.201701446
Andersen ES, Dong M, Nielsen MM, Jahn K, Subramani R, Mamdouh W, Golas MM, Sander B, Stark H, Oliveira CLP, Pedersen JS, Birkeda V, Besenbacher F, Gothelf KV, Kjems J (2009) Self-assembly of a nanoscale DNA box with a controllable lid. Nat Lett 459(7243):73–77. https://doi.org/10.1038/nature07971
Areddy PK (2011) Computer-aided design of polyhedral DNA nanostructures. KungligaTekniskaHogskolan (KTH), pp 1–27
Averick S, Paredes E, Li W, Matyjaszewski K, Das SR (2011) Direct DNA conjugation to star polymers for controlled reversible assemblies. Bioconjug Chem 22(10):2030–2037. https://doi.org/10.1021/bc200240q
Averick SE, Dey SK, Grahacharya D, Matyjaszewski K, Das SR (2014) Solid-phase incorporation of an ATRP initiator for polymer–DNA biohybrids. Angew Chem Int Ed Engl 53(10):2739–2744. https://doi.org/10.1002/anie.201308686
Boulais E, Sawaya NP, Veneziano R, Andreoni A, Banal JL, Kondo T et al (2017) Programmed coherent coupling in a synthetic DNA-based excitonic circuit. Nat Mater 17(2):1–8. https://doi.org/10.1038/nmat5033
Brglez J, Nikolov P, Angelin A, Niemeyer CM (2015) Designed intercalators for modification of DNA origami surface properties. Chem Eur J 21:9440. https://doi.org/10.1002/chem.201500086
Chang M, Yang CS, Huang DM (2011) Aptamer-conjugated DNA icosahedral nanoparticles as a carrier of doxorubicin for cancer therapy. ACS Nano 5(8):6156–6163. https://doi.org/10.1021/nn200693a
Chen J, Seeman NC (1991) Synthesis from DNA of a molecule with the connectivity of a cube. Nature 350(6319):631–633. https://doi.org/10.1038/350631a0
Chou LY, Zagorovsky K, Chan WC (2014) DNA assembly of nanoparticle superstructures for controlled biological delivery and elimination. Nat Nanotechnol 9(2):148–155. https://doi.org/10.1038/nnano.2013.309
Dietz H, Douglas HM, Shih WM (2009) Folding DNA into twisted and nanoscale shapes. Science 325(5941):725–730. https://doi.org/10.1126/science.1174251
Donald AM (2005) Self-assembly for bionanotechnology. NanoToday 56:56. https://doi.org/10.1016/S1369-7021(05)00913-2
Douglas SM, Dietz H, Lied T, Hogberg B, Graf F, Shih WM (2009a) Self-assembly of DNA into nanoscale three-dimensional shapes. Nature 459(7245):414–418. https://doi.org/10.1038/nature08016
Douglas SM, Marblestone AH, Teerapittayanon S, Vazquez A, Church GM, Shih WM (2009b) Rapid prototyping of 3D DNA-origami shapes with caDNAno. Nucleic Acids Res 37(15):5001–5006. https://doi.org/10.1093/nar/gkp436
Douglas SM, Bachelet I, Church GM (2012) A logic–gated nanorobot for targeted transport of molecular payloads. Science 335:831–834. https://doi.org/10.1126/science.1214081
Glaser M, Schnau BJ, Tschirner T, Schmidt BUS, Winkler MM, Kas JA, Smith DM (2016) Self-assembly of hierarchically ordered structures in DNA nanotube systems. New J Phys 18:055001. https://doi.org/10.1088/1367-2630/18/5/055001
Gopfrich K, Li CY, Ricci M, Bhamidimarri SP, Yoo J, Gyenes B, Ohmann A, Winterhalter M, Aksimentiev A, Keyser UF (2016) Large – conductance transmembrane porin made from DNA origami. ACS Nano 10(9):8207–8214. https://doi.org/10.1021/acsnano.6b03759
Gradisar H, Jerala R (2014) Self-assembled bionanostructures: proteins following the lead of DNA nanostructures. J Nanobiotechnol 12(4):1–9. https://doi.org/10.1186/1477-3155-12-4
Grossi G, Jepsen MD, Kjems J, Andersen ES (2017) Control of enzyme reactions by a reconfigurable DNA nanovault. Nat Commun 8(2):1–8. https://doi.org/10.1038/s41467-017-01072-8
Han D (2017) Design of wireframe DNA nanostructures – DNA gridiron. Methods Mol Biol 1500:27–40
Han D, Pal S, Nangreave J, Deng Z, Liu Y, Yan H (2011) DNA origami with complex curvatures in three-dimensional space. Science 332:342–346. https://doi.org/10.1126/science.1202998
Han D, Pal S, Yang Y, Jiang S, Nangreave J, Liu Y, Yan H (2013) DNA gridiron nanostructures based on four – arm junctions. Science 339(6126):1412–1415. https://doi.org/10.1126/science.1232252
Holliday R (1964) A mechanism for gene conversion in fungi. Genet Res 89(5):282–304. https://doi.org/10.1017/S0016672308009476
Jiang Z, Zhang S, Yang C, Kjems J, Huang Y, Besenbacher F, Dong M (2015) Serum induced degradation of 3D DNA box origami observed by high speed atomic force microscope. Nano Res 8(7):1–9. https://doi.org/10.1007/s12274-015-0724-z
Jiang DW, Sun YH, Li J, Li Q, Lv M, Zhu B, Tian T, Cheng DF, Xia YJ, Zhang L, Wang LH, Huang Q, Shi JY, Fan CH (2016) Multiple-armed tetrahedral DNA nanostructures for tumor-targeting, dual-modality in vivo imaging. ACS Appl Mater Interfaces 8(7):4378–4384. https://doi.org/10.1021/acsami.5b10792
Katsnelson A (2012) DNA robot could kill cancer cells. Nature. https://doi.org/10.1038/nature.2012.10047
Kachalova AV, Stetsenko DA, Gatib MJ, Oretskayaa TS (2004) Synthesis of oligonucleotide 2′ – conjugates via amide bond formation in solution. Bioorg Med Chem Lett 14:801–804
Ke YG, Sharma J, Liu MH, Jahn K, Liu Y, Yan H (2009) Scaffolded DNA origami of a DNA tetrahedron molecular container. Nano Lett 9(6):2445–2447. https://doi.org/10.1021/nl901165f
Kedracki D, Safir I, Gour N, Ngo KX, Nardin CV (2013) DNA – polymer conjugates: from synthesis, through complex formation and self – assembly to applications. Adv Polym Sci 253:115–150. https://doi.org/10.1007/12_2012_181
Ko S, Liu H, Chen Y, Mao C (2008) DNA nanotubes as combinatorial vehicles for cellular delivery. Biomacromolecules 9(11):3039–3043. https://doi.org/10.1021/bm800479e
Kocabey S, Meinl H, MacPherson IS, Cassinelli V, Manetto A, Rothenfusser S, Liedl T, Lichtenegger FS (2015) Cellular uptake of tile-assembled DNA nanotubes. Nano 5(1):47–60. https://doi.org/10.3390/nano5010047
Kumar V, Palazzolo S, Bayda S, Corona G, Toffoli G, Rizzolio F (2016) DNA nanotechnology for cancer therapy. Theranostics 6(5):710–725. https://doi.org/10.7150/thno.14203
Kundu A, Nandi S, Nandi AK (2017) Nucleic acid based polymer and nanoparticle conjugates: synthesis, properties and applications. Prog Mater Sci 88:136–185. https://doi.org/10.1016/j.pmatsci.2017.04.001
Kuzuya A, Kaino M, Hashizume M, Matsumoto K, Uehara T, Matsuo Y, Mitomo H, Niikura K, Ijiro K, Ohya Y (2015) Encapsulation of a gold nanoparticle in a DNA origami container. Polym J 47:177–182. https://doi.org/10.1038/pj.2014.128
Kwak M, Herrmann A (2011) Nucleic acid amphiphiles: synthesis and self – assembled nanostructures. Chem Soc Rev 40:5745–5755. https://doi.org/10.1039/C1CS15138J
Lapique N, Benenson Y (2017) Genetic programs can be compressed and autonomously decompressed in live cells. Nat Nanotechnol 13:309. https://doi.org/10.1038/s41565-017-0004-z
Le JV, Luo Y, Darcy MA, Lucas CR, Goodwin MF, Poirier MG, Castro CE (2016) Probing nucleosome stability with a DNA origami nanocaliper. ACS Nano 10:7073–7084. https://doi.org/10.1021/acsnano.6b03218
Lee JY, Okumus B, Kim DS, Ha T (2005) Extreme conformational diversity in human telomeric DNA. PNAS 102(52):18938–18943. https://doi.org/10.1073/pnas.0506144102
Lee H, Lytton Jean AR, Chen Y, Love KT, Park AI, Karagiannnis ED et al (2012) Molecularly self-assembled nucleic acid nanoparticle for targeted in vivo SiRNA delivery. Nat Nanotechnol 7(6):389–393. https://doi.org/10.1038/nnano.2012.73
Li J, Zheng C, Cansiz S, Wu CC, Xu JH, Cui C, Liu Y, Hou WJ, Wang YY, Zhang LQ, Teng IT, Yang HH, Tan WH (2015) Self-assembly of DNA nanohydrogels with controllable size and stimuli-responsive property for targeted gene regulation therapy. J Am Chem Soc 137(4):1412–1415. https://doi.org/10.1021/ja512293f
Lin C, Liu Y, Yan H (2009) Designer DNA nanoarchitectures. Biochemistry 48(8):1663–1374. https://doi.org/10.1021/bi802324w
Liu X, Xu Y, Clifford C, Liu Y, Yan H, Chang Y (2012) A DNA nanostructure platform for directed assembly of synthetic vaccines. Nano Lett 12(8):4254–4259. https://doi.org/10.1021/nl301877k
Liu M, Fu J, Hejesen C, Yang Y, Woodbury NW, Gothelf K, Liu Y, Yan H (2013) A DNA tweezer-actuated enzyme nanoreactor. Nat Commun 4:1–4. https://doi.org/10.1038/ncomms3127
Lv Y, Hu R, Zhu G, Zhang X, Mei L, Liu Q, Qiu L, Wu C, Tan W (2015) Preparation and biomedical applications of programmable and multifunctional DNA nanoflowers. Nat Protoc 10(10):1508–1524. https://doi.org/10.1038/nprot.2015.078
Ma C, Wu Z, Wang W, Jiang Q, Shi C (2015) Three-dimensional DNA nanostructures for colorimetric assay of nucleic acids. J Mater Chem B 3:2853–2857. https://doi.org/10.1039/C4TB02049A
Ma X, Huh J, Park W, Lee LP, Kwon YJ, Sim SJ (2016) Gold nanocrystals with DNA – directed morphologies. Nat Commun 7:12873. https://doi.org/10.1038/ncomms12873
Marchi AN, Saaem I, Vogen BN, Brown S, Labean TH (2014) Towards larger DNA origami. Nano 14(10):5740–5747. https://doi.org/10.1021/nl502626s
Martin TG, Dietz H (2012) Magnesium-free self-assembly of multi-layer DNA objects. Nat Commun 3:1–5. https://doi.org/10.1038/ncomms2095
Mikkila J, Eskelinen AP, Niemela EH, Linko V, Frilander MJ, Torma P, Kostiainen MA (2014) Virus – encapsulated DNA origami nanostructures for cellular delivery. Nano Lett 14(4):2196–2200. https://doi.org/10.1021/nl500677j
Modi S, Swetha MG, Goswami D, Gupta GD, Mayor S, Krishnan Y (2009) A DNA nanomachine that maps spatial and temporal pH changes inside living cells. Nat Nanotechnol 4(5):325–330. https://doi.org/10.1038/NNANO.2009.83
Perrault SD, Shih WM (2014) Virus-inspired membrane encapsulation of DNA nanostructures to achieve in vivo stability. ACS Nano 8(5):5132–5140. https://doi.org/10.1021/nn5011914
Peterson AM, Heemstra JM (2015) Controlling self-assembly of DNA-polymer conjugates for applications in imaging and drug delivery. Adv Rev 7(3):282–297. https://doi.org/10.1002/wnan.1309
Rothemund PWK (2005) Design of DNA origami. In: ICCAD 2005-international conference on computer aided design, San Jose, CA, 6–10 November 2005. IEEE, Piscataway, pp 470–477
Rothenmund PW (2006) Folding DNA to create nanoscale shapes and patterns. Nature 440(7082):297–302. https://doi.org/10.1038/nature04586
Schiffels D, Szalai VA, Liddle JA (2017) Molecular precision at micrometer length scales: Hierarchal assembly of DNA-protein nanostructures. ACS Nano 11(17):6623–6629. https://doi.org/10.1021/acsnano.7b00320
Schnitzler T, Herrmann A (2012) DNA block copolymers: functional materials for nanoscience and biomedicine. Acc Chem Res 45(9):1419–1430. https://doi.org/10.1021/ar200211a
Schüller VJ, Heidegger A, Sandholzer N, Nickels PC, Suhartha NA, Endres S, Bourquin C, Liedl T (2011) Cellular immunization by CpG-sequence coated DNA origami structures. ACS Nano 5(12):9692–9702. https://doi.org/10.1021/nn203161y
Seeman NC (1982) Nucleic acid junctions and lattices. J Theor Biol 99(2):237–247
Seeman NC (2003) DNA nanotechnology. Mater Today 6(1):24–29. https://doi.org/10.1016/S1369-7021(03)00129-9
Seeman NC (2010) Nanomaterials based on DNA. Annu Rev Biochem 79:65–87. https://doi.org/10.1146/annurev-biochem-060308-102244
Seeman NC, Kallenbatch NR (1983) Design of immobile nucleic acid junctions. Biophys J 44:201–209
Setyawati MI, Kutty RV, Leong DT (2016) DNA nanostructures carrying stoichiometrically definable antibodies. Small 12(40):5601–5611. https://doi.org/10.1002/smll.201601669
Singh Y, Murat P, Defrancq E (2010) Recent development in oligonucleotide conjugation. Chem Soc Rev 39(6):2054–2070. https://doi.org/10.1039/b911431a. Epub 2010 Apr 14
Song L, Jiang Q, Liu J, Li N, Liu Q, Dai L, Gao Y, Liu W, Liu DS, Ding B (2017) DNA origami/gold nanorod hybrid nanostructures for the circumvention of drug resistance. Nanoscale 9:7750–7754. https://doi.org/10.1039/c7nr02222k
Steinhart C, Jungman R, Sobey TL, Simmel FC, Tinnefield P (2009) DNA origami as a nanoscopic ruler for super – resolution microscopy. Angew Chem Int Ed Engl 48(47):8870–8873. https://doi.org/10.1002/anie.200903308
Subramanian R, Juul S, Rotaru A, Andersen FF, Gothelf KV, Mamdouh W, Besenbacher F, Dong M, Knudsen BR (2010) A novel secondary DNA binding site in human topoisomerase I unravelled by using a 2D DNA origami platform. ACS Nano 4(10):5969–5977. https://doi.org/10.1021/nn101662a
Sun W, Gu Z (2015) Engineering DNA scaffolds for delivery of anticancer therapeutics. Biomater Sci 3(7):1018–1024. https://doi.org/10.1039/c4bm00459k
Sun W, Gu Z (2016) ATP- responsive drug delivery systems. Expert Opin Drug Deliv 13(3):311–314. https://doi.org/10.1517/17425247.2016.1140147
Sun W, Jiang T, Lu Y, Reiff M, Mo R, Gu Z (2014a) Cocoon-like self-degradable DNA nanoclew for anticancer drug delivery. J Am Chem Soc 136(42):14722–14725. https://doi.org/10.1021/ja5088024
Sun W, Boulais E, Hakobyan Y, Wang WL, Guan A, Bathe M, Yin P (2014b) Casting inorganic structures with DNA molds. Science 346(6210):1258361. https://doi.org/10.1126/science.1258361
Sut PA, Tunc CA, Culha M (2016) Lactose modified DNA tile nanostructures as drug carriers. J Drug Target 24(8):709–719. https://doi.org/10.3109/1061186X.2016.1144059
Tian Y, Wang T, Ke Y (2015) Prescribed nanoparticle cluster architectures and low – dimensional arrays built using octahedral DNA origami frames. Nat Nanotechnol 10:637–644. https://doi.org/10.1038/nnano.2015.105
Veetil AT, Chakraborty K, Xiao K, Minter MR, Sisodia SS, Krishnan Y (2017) Cell – targetable DNA nanocapsules for spatiotemporal release of caged bioactive small molecules. Nat Nanotechnol 12:1183. https://doi.org/10.1038/nnano.2017.159
Veneziano R, Ratanalert S, Zhang F, Zhang H, Chiu W, Bathe M (2016) Designer nanoscale DNA assemblies programmed from the top down. Science 352(6293):1534. https://doi.org/10.1126/science.aaf4388
Vindigni G, Raniolo S, Ottaviani A, Falconi M, Franch O, Knudsen BR, Alessandro Desideri A, Biocca S (2016) Receptor-mediated entry of pristine octahedral DNA nanocages in mammalian cells. ACS Nano 10:5971–5979. https://doi.org/10.1021/acsnano.6b01402
Walsh S, Yin HF, Erben CM, Wood MJA, Turberfield AJ (2011) DNA cage delivery to mammalian cells. ACS Nano 5(7):5427–5432. https://doi.org/10.1021/nn2005574
Zadegan RM, Norton ML (2012) Structural DNA nanotechnology: from design to applications. Int J Mol Sci 13(6):7149–7162. https://doi.org/10.3390/ijms13067149
Zhang Y, Fu F, Yager KG, Gang O (2013) A general strategy for the DNA-mediated self – assembly of functional nanoparticles into heterogeneous systems. Nat Nanopart 8(11):865–872. https://doi.org/10.1038/nnano.2013.209
Zhang H, Ma Y, Xie Y, An Y, Huang Y, Zhu Z, Yang CJ (2015) A controllable aptamer-based self-assembled DNA dendrimer for high affinity targeting, bioimaging and drug delivery. Sci Rep 5:1–8. https://doi.org/10.1038/srep10099
Zhang P, Ye J, Liu E, Sun L, Zhang J, Lee SJ, Gong J, He H, Yang VC (2017) Aptamer – coded DNA nanoparticles for targeted doxorubicin delivery using pH – sensitive spacer. Front Chem Sci Eng:1–8. https://doi.org/10.1007/s11705-017-1645-z
Zhao YX, Shaw A, Zeng X, Benson E, Nystrom AM, Hogberg B (2012) DNA origami delivery system for cancer therapy with tunable release properties. ACS Nano 6(10):8684–8691. https://doi.org/10.1021/nn3022662
Zhu Y, Wang G, Sha L, Qiu Y, Jianga H, Zhang X (2015) A ratiometric colorimetric detection of the folate receptor based on terminal protection of small-molecule-linked DNA. Analyst 140(4):12601264. https://doi.org/10.1039/C4AN02115K
Zhua G, Zhenga J, Song E, Donovana M, Zhangb K, Liue C, Tana W (2013) Self-assembled, aptamer-tethered DNA nanotrains for targeted transport of molecular drugs in cancer theranostics. PNAS 110(20):7998–8003. https://doi.org/10.1073/pnas.1220817110
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Dilna, V., Sabu, C., Pramod, K. (2021). DNA-Based Nanopharmaceuticals. In: Yata, V., Ranjan, S., Dasgupta, N., Lichtfouse, E. (eds) Nanopharmaceuticals: Principles and Applications Vol. 1. Environmental Chemistry for a Sustainable World, vol 46. Springer, Cham. https://doi.org/10.1007/978-3-030-44925-4_4
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