Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Aptamer-Functionalized DNA Nanostructures for Biological Applications

  • 82 Accesses

Abstract

DNA nanostructures hold great promise for various applications due to their remarkable properties, including programmable assembly, nanometric positional precision, and dynamic structural control. The past few decades have seen the development of various kinds of DNA nanostructures that can be employed as useful tools in fields such as chemistry, materials, biology, and medicine. Aptamers are short single-stranded nucleic acids that bind to specific targets with excellent selectivity and high affinity and play critical roles in molecular recognition. Recently, many attempts have been made to integrate aptamers with DNA nanostructures for a range of biological applications. This review starts with an introduction to the features of aptamer-functionalized DNA nanostructures. The discussion then focuses on recent progress (particularly during the last five years) in the applications of these nanostructures in areas such as biosensing, bioimaging, cancer therapy, and biophysics. Finally, challenges involved in the practical application of aptamer-functionalized DNA nanostructures are discussed, and perspectives on future directions for research into and applications of aptamer-functionalized DNA nanostructures are provided.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13
Fig. 14
Fig. 15
Fig. 16

References

  1. 1.

    Pugazhendhi A, Shobana S, Nguyen DD, Banu JR, Sivagurunathan P, Chang SW, Ponnusamy VK, Kumar G (2019) Application of nanotechnology (nanoparticles) in dark fermentative hydrogen production. Int J Hydrogen Energy 44(3):1431–1440

  2. 2.

    Fan Y, Wang P, Lu Y, Wang R, Zhou L, Zheng X, Li X, Piper JA, Zhang F (2018) Lifetime-engineered NIR-II nanoparticles unlock multiplexed in vivo imaging. Nat Nanotechnol 13(10):941–946

  3. 3.

    Hu Q, Li H, Wang L, Gu H, Fan C (2019) DNA nanotechnology-enabled drug delivery systems. Chem Rev 119(10):6459–6506

  4. 4.

    Shulaker MM, Hills G, Park RS, Howe RT, Saraswat K, Wong HP, Mitra S (2017) Three-dimensional integration of nanotechnologies for computing and data storage on a single chip. Nature 547(7661):74–78

  5. 5.

    Seeman NC (1982) Nucleic acid junctions and lattices. J Theor Biol 99(2):237–247

  6. 6.

    Fu TJ, Seeman NC (1993) DNA double-crossover molecules. Biochemistry 32(13):3211–3220

  7. 7.

    Winfree E, Liu F, Wenzler LA, Seeman NC (1998) Design and self-assembly of two-dimensional DNA crystals. Nature 394(6693):539–544

  8. 8.

    LaBean TH, Yan H, Kopatsch J, Liu FR, Winfree E, Reif JH, Seeman NC (2000) Construction, analysis, ligation, and self-assembly of DNA triple crossover complexes. J Am Chem Soc 122(9):1848–1860

  9. 9.

    Yan H, Park SH, Finkelstein G, Reif JH, LaBean TH (2003) DNA-templated self-assembly of protein arrays and highly conductive nanowires. Science 301(5641):1882–1884

  10. 10.

    He Y, Ye T, Su M, Zhang C, Ribbe AE, Jiang W, Mao C (2008) Hierarchical self-assembly of DNA into symmetric supramolecular polyhedra. Nature 452(7184):198–201

  11. 11.

    He Y, Chen Y, Liu HP, Ribbe AE, Mao CD (2005) Self-assembly of hexagonal DNA two-dimensional (2D) arrays. J Am Chem Soc 127(35):12202–12203

  12. 12.

    Chen JH, Seeman NC (1991) Synthesis from DNA of a molecule with the connectivity of a cube. Nature 350(6319):631–633

  13. 13.

    Zhang C, Ko SH, Su M, Leng Y, Ribbe AE, Jiang W, Mao C (2009) Symmetry controls the face geometry of DNA polyhedra. J Am Chem Soc 131(4):1413–1415

  14. 14.

    Goodman RP, Schaap IAT, Tardin CF, Erben CM, Berry RM, Schmidt CF, Turberfield AJ (2005) Rapid chiral assembly of rigid DNA building blocks for molecular nanofabrication. Science 310(5754):1661–1665

  15. 15.

    Shih WM, Quispe JD, Joyce GF (2004) A 1.7-kilobase single-stranded DNA that folds into a nanoscale octahedron. Nature 427(6975):618–621

  16. 16.

    Wu X-R, Wu C-W, Ding F, Tian C, Jiang W, Mao C-D, Zhang C (2017) Binary self-assembly of highly symmetric DNA nanocages via sticky-end engineering. Chin Chem Lett 28(4):851–856

  17. 17.

    Hudson RHE, Damha MJ (1993) Nucleic acid dendrimers: novel biopolymer structures. J Am Chem Soc 115(6):2119–2124

  18. 18.

    Meng HM, Zhang XB, Lv YF, Zhao ZL, Wang NN, Fu T, Fan HH, Liang H, Qiu LP, Zhu G (2014) DNA dendrimer: an efficient nanocarrier of functional nucleic acids for intracellular molecular sensing. ACS Nano 8(6):6171–6181

  19. 19.

    Xuan F, Hsing IM (2014) Triggering hairpin-free chain-branching growth of fluorescent DNA dendrimers for nonlinear hybridization chain reaction. J Am Chem Soc 136(28):9810–9813

  20. 20.

    Song J, Arbona JM, Zhang Z, Liu L, Xie E, Elezgaray J, Aime JP, Gothelf KV, Besenbacher F, Dong M (2012) Direct visualization of transient thermal response of a DNA origami. J Am Chem Soc 134(24):9844–9847

  21. 21.

    Lu CH, Guo W, Hu Y, Qi XJ, Willner I (2015) Multitriggered shape-memory acrylamide-DNA hydrogels. J Am Chem Soc 137(50):15723–15731

  22. 22.

    Zhu G, Hu R, Zhao Z, Chen Z, Zhang X, Tan W (2013) Noncanonical self-assembly of multifunctional DNA nanoflowers for biomedical applications. J Am Chem Soc 135(44):16438–16445

  23. 23.

    Mandal S, Muller J (2017) Metal-mediated DNA assembly with ligand-based nucleosides. Curr Opin Chem Biol 37:71–79

  24. 24.

    Rothemund PWK (2006) Folding DNA to create nanoscale shapes and patterns. Nature 440(7082):297–302

  25. 25.

    English MA, Soenksen LR, Gayet RV, de Puig H, Angenent-Mari NM, Mao AS, Nguyen PQ, Collins JJ (2019) Programmable CRISPR-responsive smart materials. Science 365(6455):780–785

  26. 26.

    Shao Y, Jia H, Cao T, Liu D (2017) Supramolecular hydrogels based on DNA self-assembly. Acc Chem Res 50(4):659–668

  27. 27.

    Wang J, Chao J, Liu H, Su S, Wang L, Huang W, Willner I, Fan C (2017) Clamped hybridization chain reactions for the self-assembly of patterned DNA hydrogels. Angew Chem Int Ed Engl 56(8):2171–2175

  28. 28.

    Lim KS, Lee DY, Valencia GM, Won Y-W, Bull DA (2015) Nano-self-assembly of nucleic acids capable of transfection without a gene carrier. Adv Funct Mater 25(34):5445–5451

  29. 29.

    Dong Y, Chen S, Zhang S, Sodroski J, Yang Z, Liu D, Mao Y (2018) Folding DNA into a lipid-conjugated nanobarrel for controlled reconstitution of membrane proteins. Angew Chem Int Ed Engl 57(8):2072–2076

  30. 30.

    Zhang K, Zhu X, Jia F, Auyeung E, Mirkin CA (2013) Temperature-activated nucleic acid nanostructures. J Am Chem Soc 135(38):14102–14105

  31. 31.

    Amodio A, Adedeji AF, Castronovo M, Franco E, Ricci F (2016) pH-controlled assembly of DNA tiles. J Am Chem Soc 138(39):12735–12738

  32. 32.

    Zhu B, Zhao Y, Dai JB, Wang JB, Xing S, Guo LJ, Chen N, Qu XM, Li L, Shen JW, Shi JY, Li J, Wang LH (2017) Preservation of DNA nanostructure carriers: effects of freeze-thawing and ionic strength during lyophilization and storage. ACS Appl Mater Interfaces 9(22):18434–18439

  33. 33.

    Zhou W, Saran R, Liu J (2017) Metal sensing by DNA. Chem Rev 117(12):8272–8325

  34. 34.

    Silverman SK (2016) Catalytic DNA: scope, applications, and biochemistry of deoxyribozymes. Trends Biochem Sci 41(7):595–609

  35. 35.

    Li D, Song S, Fan C (2010) Target-responsive structural switching for nucleic acid-based sensors. Acc Chem Res 43(5):631–641

  36. 36.

    Surana S, Shenoy AR, Krishnan Y (2015) Designing DNA nanodevices for compatibility with the immune system of higher organisms. Nat Nanotechnol 10(9):741–747

  37. 37.

    Zhu G, Zheng J, Song E, Donovan M, Zhang K, Liu C, Tan W (2013) Self-assembled, aptamer-tethered DNA nanotrains for targeted transport of molecular drugs in cancer theranostics. Proc Natl Acad Sci USA 110(20):7998–8003

  38. 38.

    Zhou Y, Tang L, Zeng G, Zhang C, Zhang Y, Xie X (2016) Current progress in biosensors for heavy metal ions based on DNAzymes/DNA molecules functionalized nanostructures: a review. Sens Actuators B Chem 223:280–294

  39. 39.

    Xie N, Huang J, Yang X, Yang Y, Quan K, Wang H, Ying L, Ou M, Wang K (2016) A DNA tetrahedron-based molecular beacon for tumor-related mRNA detection in living cells. Chem Commun 52(11):2346–2349

  40. 40.

    Tuerk C, Gold L (1990) Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249(4968):505–510

  41. 41.

    Robertson DL, Joyce GF (1990) Selection in vitro of an RNA enzyme that specifically cleaves single-stranded DNA. Nature 344(6265):467–468

  42. 42.

    Ellington AD, Szostak JW (1990) In vitro selection of RNA molecules that bind specific ligands. Nature 346(6287):818–822

  43. 43.

    Lu D, He L, Zhang G, Lv A, Wang R, Zhang X, Tan W (2017) Aptamer-assembled nanomaterials for fluorescent sensing and imaging. Nanophotonics 6(1):109–121

  44. 44.

    Olaru A, Bala C, Jaffrezic-Renault N, Aboul-Enein HY (2015) Surface plasmon resonance (SPR) biosensors in pharmaceutical analysis. Crit Rev Anal Chem 45(2):97–105

  45. 45.

    Jayanthi V, Das AB, Saxena U (2017) Recent advances in biosensor development for the detection of cancer biomarkers. Biosens Bioelectron 91:15–23

  46. 46.

    Dong Y, Xu Y, Yong W, Chu X, Wang D (2014) Aptamer and its potential applications for food safety. Crit Rev Food Sci Nutr 54(12):1548–1561

  47. 47.

    Nguyen P-L, Sekhon SS, Ahn J-Y, Ko JH, Lee L, Cho S-J, Min J, Kim Y-H (2017) Aptasensor for environmental monitoring. Toxicol Environ Health Sci 9(2):89–101

  48. 48.

    Chen Y, Zhou S, Li L, Zhu J-j (2017) Nanomaterials-based sensitive electrochemiluminescence biosensing. Nano Today 12:98–115

  49. 49.

    Munzar JD, Ng A, Juncker D (2019) Duplexed aptamers: history, design, theory, and application to biosensing. Chem Soc Rev 48(5):1390–1419

  50. 50.

    Meng HM, Liu H, Kuai H, Peng R, Mo L, Zhang XB (2016) Aptamer-integrated DNA nanostructures for biosensing, bioimaging and cancer therapy. Chem Soc Rev 45(9):2583–2602

  51. 51.

    Huang R, He N, Li Z (2018) Recent progresses in DNA nanostructure-based biosensors for detection of tumor markers. Biosens Bioelectron 109:27–34

  52. 52.

    Lin M, Song P, Zhou G, Zuo X, Aldalbahi A, Lou X, Shi J, Fan C (2016) Electrochemical detection of nucleic acids, proteins, small molecules and cells using a DNA-nanostructure-based universal biosensing platform. Nat Protoc 11(7):1244–1263

  53. 53.

    Liu M, Zhang Q, Kannan B, Botton GA, Yang J, Soleymani L, Brennan JD, Li Y (2018) Self-assembled functional DNA superstructures as high-density and versatile recognition elements for printed paper sensors. Angew Chem Int Ed Engl 57(38):12440–12443

  54. 54.

    Li Z, Zhao B, Wang D, Wen Y, Liu G, Dong H, Song S, Fan C (2014) DNA nanostructure-based universal microarray platform for high-efficiency multiplex bioanalysis in biofluids. ACS Appl Mater Interfaces 6(20):17944–17953

  55. 55.

    Walter HK, Bauer J, Steinmeyer J, Kuzuya A, Niemeyer CM, Wagenknecht HA (2017) “DNA Origami Traffic Lights” with a split aptamer sensor for a bicolor fluorescence readout. Nano Lett 17(4):2467–2472

  56. 56.

    Peng P, Shi L, Wang H, Li T (2017) A DNA nanoswitch-controlled reversible nanosensor. Nucleic Acids Res 45(2):541–546

  57. 57.

    Tang MSL, Shiu SC, Godonoga M, Cheung YW, Liang S, Dirkzwager RM, Kinghorn AB, Fraser LA, Heddle JG, Tanner JA (2018) An aptamer-enabled DNA nanobox for protein sensing. Nanomedicine 14(4):1161–1168

  58. 58.

    Wang J, Dong HY, Zhou Y, Han LY, Zhang T, Lin M, Wang C, Xu H, Wu ZS, Jia L (2018) Immunomagnetic antibody plus aptamer pseudo-DNA nanocatenane followed by rolling circle amplication for highly-sensitive CTC detection. Biosens Bioelectron 122:239–246

  59. 59.

    Walsh AS, Yin H, Erben CM, Wood MJ, Turberfield AJ (2011) DNA cage delivery to mammalian cells. ACS Nano 5(7):5427–5432

  60. 60.

    Zheng X, Peng R, Jiang X, Wang Y, Xu S, Ke G, Fu T, Liu Q, Huan S, Zhang X (2017) Fluorescence resonance energy transfer-based DNA nanoprism with a split aptamer for adenosine triphosphate sensing in living cells. Anal Chem 89(20):10941–10947

  61. 61.

    Zhong L, Cai S, Huang Y, Yin L, Yang Y, Lu C, Yang H (2018) DNA octahedron-based fluorescence nanoprobe for dual tumor-related mRNAs detection and imaging. Anal Chem 90(20):12059–12066

  62. 62.

    Jie G, Gao X, Ge J, Li C (2019) Multifunctional DNA nanocage with CdTe quantum dots for fluorescence detection of human 8-oxoG DNA glycosylase 1 and doxorubicin delivery to cancer cells. Mikrochim Acta 186(2):85

  63. 63.

    Topkaya SN, Azimzadeh M, Ozsoz M (2016) Electrochemical biosensors for cancer biomarkers detection: recent advances and challenges. Electroanalysis 28(7):1402–1419

  64. 64.

    Hasanzadeh M, Shadjou N, de la Guardia M (2017) Early stage screening of breast cancer using electrochemical biomarker detection. Trends Anal Chem 91:67–76

  65. 65.

    Zeng Y, Zhu Z, Du D, Lin Y (2016) Nanomaterial-based electrochemical biosensors for food safety. J Electroanal Chem (Lausanne) 781:147–154

  66. 66.

    Mazzei F, Favero G, Bollella P, Tortolini C, Mannina L, Conti ME, Antiochia R (2015) Recent trends in electrochemical nanobiosensors for environmental analysis. Int J Environ Health 7(3):267–291

  67. 67.

    Yang J, Dou B, Yuan R, Xiang Y (2017) Aptamer/protein proximity binding-triggered molecular machine for amplified electrochemical sensing of thrombin. Anal Chem 89(9):5138–5143

  68. 68.

    Yang J, Dou B, Yuan R, Xiang Y (2016) Proximity binding and metal ion-dependent DNAzyme cyclic amplification-integrated aptasensor for label-free and sensitive electrochemical detection of thrombin. Anal Chem 88(16):8218–8223

  69. 69.

    Jiang B, Li F, Yang C, Xie J, Xiang Y, Yuan R (2015) Aptamer pseudoknot-functionalized electronic sensor for reagentless and single-step detection of immunoglobulin E in human serum. Anal Chem 87(5):3094–3098

  70. 70.

    Pei H, Lu N, Wen Y, Song S, Liu Y, Yan H, Fan C (2010) A DNA nanostructure-based biomolecular probe carrier platform for electrochemical biosensing. Adv Mater 22(42):4754–4758

  71. 71.

    Sun D, Luo Z, Lu J, Zhang S, Che T, Chen Z, Zhang L (2019) Electrochemical dual-aptamer-based biosensor for nonenzymatic detection of cardiac troponin I by nanohybrid electrocatalysts labeling combined with DNA nanotetrahedron structure. Biosens Bioelectron 134:49–56

  72. 72.

    Wei M, Zhang W (2018) Ultrasensitive aptasensor with DNA tetrahedral nanostructure for ochratoxin A detection based on hemin/G-quadruplex catalyzed polyaniline deposition. Sens Actuators B Chem 276:1–7

  73. 73.

    Sun D, Lu J, Chen D, Jiang Y, Wang Z, Qin W, Yu Y, Chen Z, Zhang Y (2018) Label-free electrochemical detection of HepG2 tumor cells with a self-assembled DNA nanostructure-based aptasensor. Sens Actuators B Chem 268:359–367

  74. 74.

    Fan J, Liu Y, Xu E, Zhang Y, Wei W, Yin L, Pu Y, Liu S (2016) A label-free ultrasensitive assay of 8-hydroxy-2′-deoxyguanosine in human serum and urine samples via polyaniline deposition and tetrahedral DNA nanostructure. Anal Chim Acta 946:48–55

  75. 75.

    Poturnayová A, Šnejdárková M, Castillo G, Rybár P, Leitner M, Ebner A, Hianik T (2015) Aptamer-based detection of thrombin by acoustic method using DNA tetrahedrons as immobilisation platform. Chem Pap 69(1):221–226

  76. 76.

    Melo SA, Sugimoto H, O’Connell JT, Kato N, Villanueva A, Vidal A, Qiu L, Vitkin E, Perelman LT, Melo CA (2014) Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis. Cancer Cell 26(5):707–721

  77. 77.

    Wang S, Zhang L, Wan S, Cansiz S, Cui C, Liu Y, Cai R, Hong C, Teng IT, Shi M, Wu Y, Dong Y, Tan W (2017) Aptasensor with expanded nucleotide using DNA nanotetrahedra for electrochemical detection of cancerous exosomes. ACS Nano 11(4):3943–3949

  78. 78.

    Peng G, Li X, Cui F, Qiu Q, Chen X, Huang H (2018) Aflatoxin B1 electrochemical aptasensor based on tetrahedral DNA nanostructures functionalized three dimensionally ordered macroporous MoS2-AuNPs film. ACS Appl Mater Interfaces 10(21):17551–17559

  79. 79.

    Peng K, Zhao H, Xie P, Hu S, Yuan Y, Yuan R, Wu X (2016) Impedimetric aptasensor for nuclear factor kappa B with peroxidase-like mimic coupled DNA nanoladders as enhancer. Biosens Bioelectron 81:1–7

  80. 80.

    Taghdisi SM, Danesh NM, Nameghi MA, Ramezani M, Alibolandi M, Abnous K (2019) An electrochemical sensing platform based on ladder-shaped DNA structure and label-free aptamer for ultrasensitive detection of ampicillin. Biosens Bioelectron 133:230–235

  81. 81.

    Zhao G, Ding J, Yu H, Yin T, Qin W (2016) Potentiometric aptasensing of Vibrio alginolyticus based on DNA nanostructure-modified magnetic beads. Sensors (Basel) 16(12):2052

  82. 82.

    Xie S, Dong Y, Yuan Y, Chai Y, Yuan R (2016) Ultrasensitive lipopolysaccharides detection based on doxorubicin conjugated N-(aminobutyl)-N-(ethylisoluminol) as electrochemiluminescence indicator and self-assembled tetrahedron DNA dendrimers as nanocarriers. Anal Chem 88(10):5218–5224

  83. 83.

    Wang YH, Chen YX, Wu X, Huang KJ (2018) Electrochemical biosensor based on Se-doped MWCNTs-graphene and Y-shaped DNA-aided target-triggered amplification strategy. Colloids Surf B Biointerfaces 172:407–413

  84. 84.

    Ge J, Zhao Y, Li C, Jie G (2019) Versatile electrochemiluminescence and electrochemical “on-off” assays of methyltransferases and aflatoxin B1 based on a novel multifunctional DNA nanotube. Anal Chem 91(5):3546–3554

  85. 85.

    Sheng Q, Liu R, Zhang S, Zheng J (2014) Ultrasensitive electrochemical cocaine biosensor based on reversible DNA nanostructure. Biosens Bioelectron 51:191–194

  86. 86.

    Lee T, Park SY, Jang H, Kim GH, Lee Y, Park C, Mohammadniaei M, Lee MH, Min J (2019) Fabrication of electrochemical biosensor consisted of multi-functional DNA structure/porous Au nanoparticle for avian influenza virus (H5N1) in chicken serum. Mater Sci Eng C Mater Biol Appl 99:511–519

  87. 87.

    Song Y, Wei W, Qu X (2011) Colorimetric biosensing using smart materials. Adv Mater 23(37):4215–4236

  88. 88.

    Fahimi-Kashani N, Hormozi-Nezhad MR (2016) Gold-nanoparticle-based colorimetric sensor array for discrimination of organophosphate pesticides. Anal Chem 88(16):8099–8106

  89. 89.

    Zhou L, Sun N, Xu L, Chen X, Cheng H, Wang J, Pei R (2016) Dual signal amplification by an “on-command” pure DNA hydrogel encapsulating HRP for colorimetric detection of ochratoxin A. RSC Adv 6(115):114500–114504

  90. 90.

    Sun QK, Chen MS, Liu ZW, Zhang HC, Yang WJ (2017) Efficient colorimetric fluoride anion chemosensors based-on simple naphthodipyrrolidone dyes. Tetrahedron Lett 58(28):2711–2714

  91. 91.

    Deng J, Ma W, Yu P, Mao L (2015) Colorimetric and fluorescent dual mode sensing of alcoholic strength in spirit samples with stimuli-responsive infinite coordination polymers. Anal Chem 87(13):6958–6965

  92. 92.

    Yin BC, Ye BC, Wang H, Zhu Z, Tan W (2012) Colorimetric logic gates based on aptamer-crosslinked hydrogels. Chem Commun (Camb) 48(9):1248–1250

  93. 93.

    Ghosh SK, Pal T (2007) Interparticle coupling effect on the surface plasmon resonance of gold nanoparticles: from theory to applications. Chem Rev 107(11):4797–4862

  94. 94.

    Liu J, Lu Y (2006) Preparation of aptamer-linked gold nanoparticle purple aggregates for colorimetric sensing of analytes. Nat Protoc 1(1):246–252

  95. 95.

    Yang H, Liu H, Kang H, Tan W (2008) Engineering target-responsive hydrogels based on aptamer-target interactions. J Am Chem Soc 130(20):6320–6321

  96. 96.

    Li J, Mo L, Lu CH, Fu T, Yang HH, Tan W (2016) Functional nucleic acid-based hydrogels for bioanalytical and biomedical applications. Chem Soc Rev 45(5):1410–1431

  97. 97.

    Oishi M, Nakatani K (2019) Dynamically programmed switchable DNA hydrogels based on a DNA circuit mechanism. Small 15(15):e1900490

  98. 98.

    Liu J, Mazumdar D, Lu Y (2006) A simple and sensitive “dipstick” test in serum based on lateral flow separation of aptamer-linked nanostructures. Angew Chem Int Ed Engl 45(47):7955–7959

  99. 99.

    Wei X, Tian T, Jia S, Zhu Z, Ma Y, Sun J, Lin Z, Yang CJ (2015) Target-responsive DNA hydrogel mediated “stop-flow” microfluidic paper-based analytic device for rapid, portable and visual detection of multiple targets. Anal Chem 87(8):4275–4282

  100. 100.

    Shi D, Sun Y, Lin L, Shi C, Wang G, Zhang X (2016) Naked-eye sensitive detection of alkaline phosphatase (ALP) and pyrophosphate (PPi) based on a horseradish peroxidase catalytic colorimetric system with Cu(II). Analyst 141(19):5549–5554

  101. 101.

    Xu J, Qian J, Li H, Wu Z-S, Shen W, Jia L (2016) Intelligent DNA machine for the ultrasensitive colorimetric detection of nucleic acids. Biosens Bioelectron 75:41–47

  102. 102.

    Ravan H (2016) Isothermal RNA detection through the formation of DNA concatemers containing HRP-mimicking DNAzymes on the surface of gold nanoparticles. Biosens Bioelectron 80:67–73

  103. 103.

    Norouzi A, Ravan H, Mohammadi A, Hosseinzadeh E, Norouzi M, Fozooni T (2018) Aptamer-integrated DNA nanoassembly: a simple and sensitive DNA framework to detect cancer cells. Anal Chim Acta 1017:26–33

  104. 104.

    Wu N, Willner I (2017) Programmed dissociation of dimer and trimer origami structures by aptamer-ligand complexes. Nanoscale 9(4):1416–1422

  105. 105.

    Daems D, Pfeifer W, Rutten I, Sacca B, Spasic D, Lammertyn J (2018) Three-dimensional DNA origami as programmable anchoring points for bioreceptors in fiber optic surface plasmon resonance biosensing. ACS Appl Mater Interfaces 10(28):23539–23547

  106. 106.

    Fang W, Jia S, Chao J, Wang L, Duan X, Liu H, Li Q, Zuo X, Wang L, Wang L, Liu N, Fan C (2019) Quantizing single-molecule surface-enhanced Raman scattering with DNA origami metamolecules. Sci Adv 5(9):eaau4506

  107. 107.

    Sun Y, Xu F, Zhang Y, Shi Y, Wen Z, Li Z (2011) Metallic nanostructures assembled by DNA and related applications in surface-enhancement Raman scattering (SERS) detection. J Mater Chem B 21(42):16675–16685

  108. 108.

    Huang Y, Nguyen MK, Natarajan AK, Nguyen VH, Kuzyk A (2018) A DNA origami-based chiral plasmonic sensing device. ACS Appl Mater Interfaces 10(51):44221–44225

  109. 109.

    Funck T, Liedl T, Bae W (2019) Dual aptamer-functionalized 3D plasmonic metamolecule for thrombin sensing. Appl Sci 9(15):3006

  110. 110.

    Koirala D, Shrestha P, Emura T, Hidaka K, Mandal S, Endo M, Sugiyama H, Mao H (2014) Single-molecule mechanochemical sensing using DNA origami nanostructures. Angew Chem Int Ed Engl 53(31):8137–8141

  111. 111.

    Lu Z, Wang Y, Xu D, Pang L (2017) Aptamer-tagged DNA origami for spatially addressable detection of aflatoxin B1. Chem Commun (Camb) 53(5):941–944

  112. 112.

    Wu C, Chen T, Han D, You M, Peng L, Cansiz S, Zhu G, Li C, Xiong X, Jimenez E (2013) Engineering of switchable aptamer micelle flares for molecular imaging in living cells. ACS Nano 7(7):5724–5731

  113. 113.

    Pei H, Liang L, Yao G, Li J, Huang Q, Fan C (2012) Reconfigurable three-dimensional DNA nanostructures for the construction of intracellular logic sensors. Angew Chem Int Ed Engl 51(36):9020–9024

  114. 114.

    Peng P, Du Y, Zheng J, Wang H, Li T (2019) Reconfigurable bioinspired framework nucleic acid nanoplatform dynamically manipulated in living cells for subcellular imaging. Angew Chem Int Ed Engl 58(6):1648–1653

  115. 115.

    Du Y, Peng P, Li T (2019) DNA logic operations in living cells utilizing lysosome-recognizing framework nucleic acid nanodevices for subcellular imaging. ACS Nano 13:5778–5784

  116. 116.

    Fan Z, Sun L, Huang Y, Wang Y, Zhang M (2016) Bioinspired fluorescent dipeptide nanoparticles for targeted cancer cell imaging and real-time monitoring of drug release. Nat Nanotechnol 11(4):388–394

  117. 117.

    Tian J, Ding L, Ju H, Yang Y, Li X, Shen Z, Zhu Z, Yu JS, Yang CJ (2014) A multifunctional nanomicelle for real-time targeted imaging and precise near-infrared cancer therapy. Angew Chem Int Ed Engl 53(36):9544–9549

  118. 118.

    Hu R, Zhang X, Zhao Z, Zhu G, Chen T, Fu T, Tan W (2014) DNA nanoflowers for multiplexed cellular imaging and traceable targeted drug delivery. Angew Chem Int Ed Engl 53(23):5821–5826

  119. 119.

    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 5:10099

  120. 120.

    Li X, Figg CA, Wang R, Jiang Y, Lyu Y, Sun H, Liu Y, Wang Y, Teng IT, Hou W, Cai R, Cui C, Li L, Pan X, Sumerlin BS, Tan W (2018) Cross-linked aptamer-lipid micelles for excellent stability and specificity in target-cell recognition. Angew Chem Int Ed Engl 57(36):11589–11593

  121. 121.

    Li J, Hong CY, Wu SX, Liang H, Wang LP, Huang G, Chen X, Yang HH, Shangguan D, Tan W (2015) Facile phase transfer and surface biofunctionalization of hydrophobic nanoparticles using Janus DNA tetrahedron nanostructures. J Am Chem Soc 137(35):11210–11213

  122. 122.

    Han X, Jiang Y, Li S, Zhang Y, Ma X, Wu Z, Wu Z, Qi X (2018) Multivalent aptamer-modified tetrahedral DNA nanocage demonstrates high selectivity and safety for anti-tumor therapy. Nanoscale 11(1):339–347

  123. 123.

    Allen TM (2002) Ligand-targeted therapeutics in anticancer therapy. Nat Rev Cancer 2(10):750

  124. 124.

    Zhang X-Q, Xu X, Lam R, Giljohann D, Ho D, Mirkin CA (2011) Strategy for increasing drug solubility and efficacy through covalent attachment to polyvalent DNA–nanoparticle conjugates. ACS Nano 5(9):6962–6970

  125. 125.

    Portugal J, Barcelo F (2016) Noncovalent binding to DNA: still a target in developing anticancer agents. Curr Med Chem 23(36):4108–4134

  126. 126.

    Da Pieve C, Blackshaw E, Missailidis S, Perkins AC (2012) PEGylation and biodistribution of an anti-MUC1 aptamer in MCF-7 tumor-bearing mice. Bioconjug Chem 23(7):1377–1381

  127. 127.

    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

  128. 128.

    Liu Q, Wang D, Xu Z, Huang C, Zhang C, He B, Mao C, Wang G, Qian H (2019) Targeted delivery of Rab26 siRNA with precisely tailored DNA prism for lung cancer therapy. ChemBioChem 20(9):1139–1144

  129. 129.

    Tian Y, Huang Y, Gao P, Chen T (2018) Nucleus-targeted DNA tetrahedron as a nanocarrier of metal complexes for enhanced glioma therapy. Chem Commun (Camb) 54(68):9394–9397

  130. 130.

    Song L, Jiang Q, Liu J, Li N, Liu Q, Dai L, Gao Y, Liu W, Liu D, Ding B (2017) DNA origami/gold nanorod hybrid nanostructures for the circumvention of drug resistance. Nanoscale 9(23):7750–7754

  131. 131.

    Li N, Wang X-Y, Xiang M-H, Liu J-W, Yu R-Q, Jiang J-H (2019) Programmable self-assembly of protein-scaffolded DNA nanohydrogels for tumor-targeted imaging and therapy. Anal Chem 91(4):2610–2614

  132. 132.

    Bates PJ, Laber DA, Miller DM, Thomas SD, Trent JO (2009) Discovery and development of the G-rich oligonucleotide AS1411 as a novel treatment for cancer. Exp Mol Pathol 86(3):151–164

  133. 133.

    Rosenberg JE, Bambury RM, Van Allen EM, Drabkin HA, Lara PN, Harzstark AL, Wagle N, Figlin RA, Smith GW, Garraway LA (2014) A phase II trial of AS1411 (a novel nucleolin-targeted DNA aptamer) in metastatic renal cell carcinoma. Investig New Drugs 32(1):178–187

  134. 134.

    Holmboe S, Hansen PL, Thisgaard H, Block I, Müller C, Langkjaer N, Høilund-Carlsen PF, Olsen BB, Mollenhauer J (2017) Evaluation of somatostatin and nucleolin receptors for therapeutic delivery in non-small cell lung cancer stem cells applying the somatostatin-analog DOTATATE and the nucleolin-targeting aptamer AS1411. PLoS One 12(5):e0178286

  135. 135.

    Zhan Y, Ma W, Zhang Y, Mao C, Shao X, Xie X, Wang F, Liu X, Li Q, Lin Y (2019) DNA-based nanomedicine with yargeting and enhancement of therapeutic efficacy of breast cancer cells. ACS Appl Mater Interfaces 11(17):15354–15365

  136. 136.

    Shangguan D, Cao Z, Meng L, Mallikaratchy P, Sefah K, Wang H, Li Y, Tan W (2008) Cell-specific aptamer probes for membrane protein elucidation in cancer cells. J Proteome Res 7(5):2133–2139

  137. 137.

    Wang J, Wang H, Wang H, He S, Li R, Deng Z, Liu X, Wang F (2019) Nonviolent self-catabolic DNAzyme nanosponges for smart anticancer drug delivery. ACS Nano 13(5):5852–5863

  138. 138.

    Sun P, Zhang N, Tang Y, Yang Y, Zhou J, Zhao Y (2018) Site-specific anchoring aptamer C2NP on DNA origami nanostructures for cancer treatment. RSC Adv 8(46):26300–26308

  139. 139.

    Parekh P, Kamble S, Zhao N, Zeng Z, Portier BP, Zu Y (2013) Immunotherapy of CD30-expressing lymphoma using a highly stable ssDNA aptamer. Biomaterials 34(35):8909–8917

  140. 140.

    Li H, Zhang K, Pi F, Guo S, Shlyakhtenko L, Chiu W, Shu D, Guo P (2016) Controllable self-assembly of RNA tetrahedrons with precise shape and size for cancer targeting. Adv Mater 28(34):7501–7507

  141. 141.

    Ma W, Zhan Y, Zhang Y, Shao X, Xie X, Mao C, Cui W, Li Q, Shi J, Li J, Fan C, Lin Y (2019) An intelligent DNA nanorobot with in vitro enhanced protein lysosomal degradation of HER2. Nano Lett 19(7):4505–4517

  142. 142.

    Chen J, Keltner L, Christopherson J, Zheng F, Krouse M, Singhal A, Wang SS (2002) New technology for deep light distribution in tissue for phototherapy. Cancer J 8(2):154–163

  143. 143.

    Agostinis P, Berg K, Cengel KA, Foster TH, Girotti AW, Gollnick SO, Hahn SM, Hamblin MR, Juzeniene A, Kessel D, Korbelik M, Moan J, Mroz P, Nowis D, Piette J, Wilson BC, Golab J (2011) Photodynamic therapy of cancer: an update. CA Cancer J Clin 61(4):250–281

  144. 144.

    Chen N, Qin S, Yang X, Wang Q, Huang J, Wang K (2016) “Sense-and-treat” DNA nanodevice for synergetic destruction of circulating tumor cells. ACS Appl Mater Interfaces 8(40):26552–26558

  145. 145.

    Jin H, Kim MG, Ko SB, Kim DH, Lee BJ, Macgregor RB Jr, Shim G, Oh YK (2018) Stemmed DNA nanostructure for the selective delivery of therapeutics. Nanoscale 10(16):7511–7518

  146. 146.

    Yen-An S, Shu-Jyuan Y, Ming-Feng W, Ming-Jium S (2010) Aptamer-based tumor-targeted drug delivery for photodynamic therapy. ACS Nano 4(3):1433–1442

  147. 147.

    Brummelkamp TR, Bernards R, Agami R (2002) A system for stable expression of short interfering RNAs in mammalian cells. Science 296(5567):550–553

  148. 148.

    Li J, Zheng C, Cansiz S, Wu C, Xu J, Cui C, Liu Y, Hou W, Wang Y, Zhang L, Teng IT, Yang HH, Tan W (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

  149. 149.

    Ren K, Liu Y, Wu J, Zhang Y, Zhu J, Yang M, Ju H (2016) A DNA dual lock-and-key strategy for cell-subtype-specific siRNA delivery. Nat Commun 7:13580

  150. 150.

    Liu J, Song L, Liu S, Zhao S, Jiang Q, Ding B (2018) A tailored DNA nanoplatform for synergistic RNAi-/chemotherapy of multidrug-resistant tumors. Angew Chem Int Ed Engl 57(47):15486–15490

  151. 151.

    Liu J, Song L, Liu S, Jiang Q, Liu Q, Li N, Wang ZG, Ding B (2018) A DNA-based nanocarrier for efficient gene delivery and combined cancer therapy. Nano Lett 18(6):3328–3334

  152. 152.

    Biswas A, Joo KI, Liu J, Zhao M, Fan G, Wang P, Gu Z, Tang Y (2011) Endoprotease-mediated intracellular protein delivery using nanocapsules. ACS Nano 5(2):1385

  153. 153.

    Ran M, Tianyue J, Jin D, Wanyi T, Zhen G (2014) Emerging micro- and nanotechnology based synthetic approaches for insulin delivery. Chem Soc Rev 43(10):3595–3629

  154. 154.

    Yang W, Xia Y, Zou Y, Meng F, Zhang J, Zhong Z (2017) Bioresponsive chimaeric nanopolymersomes enable targeted and efficacious protein therapy for human lung cancers in vivo. Chem Mater 29(20):8757–8765

  155. 155.

    Li S, Jiang Q, Liu S, Zhang Y, Tian Y, Song C, Wang J, Zou Y, Anderson GJ, Han JY, Chang Y, Liu Y, Zhang C, Chen L, Zhou G, Nie G, Yan H, Ding B, Zhao Y (2018) A DNA nanorobot functions as a cancer therapeutic in response to a molecular trigger in vivo. Nat Biotechnol 36(3):258–264

  156. 156.

    Chen Q, Zhou S, Li C, Guo Q, Yang X, Huang J, Liu J, Wang K (2019) DNA supersandwich assemblies as artificial receptors to mediate intracellular delivery of catalase for efficient ROS scavenging. Chem Commun (Camb) 55(29):4242–4245

  157. 157.

    Kim J, Kim D, Lee JB (2017) DNA aptamer-based carrier for loading proteins and enhancing the enzymatic activity. RSC Adv 7(3):1643–1645

  158. 158.

    Brody EN, Gold L (2000) Aptamers as therapeutic and diagnostic agents. J Biotechnol 74(1):5–13

  159. 159.

    Sridharan S, Weiwei C, Spicer EK, Nigel CL, Fernandes DJ (2008) The nucleolin targeting aptamer AS1411 destabilizes Bcl-2 messenger RNA in human breast cancer cells. Cancer Res 68(7):2358

  160. 160.

    Bock LC, Griffin LC, Latham JA, Vermaas EH, Toole JJ (1992) Selection of single-stranded DNA molecules that bind and inhibit human thrombin. Nature 355(6360):564

  161. 161.

    Roloff A, Carlini AS, Callmann CE, Gianneschi NC (2017) Micellar thrombin-binding aptamers: reversible nanoscale anticoagulants. J Am Chem Soc 139(46):16442–16445

  162. 162.

    Rinker S, Ke Y, Liu Y, Chhabra R, Yan H (2008) Self-assembled DNA nanostructures for distance-dependent multivalent ligand-protein binding. Nat Nanotechnol 3(7):418–422

  163. 163.

    Tintore M, Gallego I, Manning B, Eritja R, Fabrega C (2013) DNA origami as a DNA repair nanosensor at the single-molecule level. Angew Chem Int Ed Engl 52(30):7747–7750

  164. 164.

    Kumar N, Seminario JM (2018) Molecular dynamics study of thrombin capture by aptamers TBA26 and TBA29 coupled to a DNA origami. Mol Simul 44(9):749–756

  165. 165.

    Takeuchi Y, Endo M, Suzuki Y, Hidaka K, Durand G, Dausse E, Toulme JJ, Sugiyama H (2016) Single-molecule observations of RNA-RNA kissing interactions in a DNA nanostructure. Biomater Sci 4(1):130–135

  166. 166.

    Lin Y, Jiang L, Huang Y, Yang Y, He Y, Lu C, Yang H (2019) DNA-mediated reversible capture and release of circulating tumor cells with a multivalent dual-specific aptamer coating network. Chem Commun (Camb) 55(37):5387–5390

  167. 167.

    Liu Z, Tian C, Yu J, Li Y, Jiang W, Mao C (2015) Self-assembly of responsive multilayered DNA nanocages. J Am Chem Soc 137(5):1730–1733

  168. 168.

    Simon AJ, Walls-Smith LT, Freddi MJ, Fong FY, Gubala V, Plaxco KW (2017) Simultaneous measurement of the dissolution kinetics of responsive DNA hydrogels at multiple length scales. ACS Nano 11(1):461–468

  169. 169.

    Fern J, Schulman R (2018) Modular DNA strand-displacement controllers for directing material expansion. Nat Commun 9(1):3766

  170. 170.

    Zhao Z, Fan H, Zhou G, Bai H, Liang H, Wang R, Zhang X, Tan W (2014) Activatable fluorescence/MRI bimodal platform for tumor cell imaging via MnO2 nanosheet–aptamer nanoprobe. J Am Chem Soc 136(32):11220–11223

  171. 171.

    Kuai H, Zhao Z, Mo L, Liu H, Hu X, Fu T, Zhang X, Tan W (2017) Circular bivalent aptamers enable in vivo stability and recognition. J Am Chem Soc 139(27):9128–9131

  172. 172.

    Zhang F, Yan H (2017) DNA self-assembly scaled up. Nature 552(7683):34–35

  173. 173.

    Han D, Qi X, Myhrvold C, Wang B, Dai M, Jiang S, Bates M, Liu Y, An B, Zhang F, Yan H, Yin P (2017) Single-stranded DNA and RNA origami. Science 358(6369):eaao2648

  174. 174.

    Praetorius F, Kick B, Behler KL, Honemann MN, Weuster-Botz D, Dietz H (2017) Biotechnological mass production of DNA origami. Nature 552(7683):84–87

  175. 175.

    Mathur D, Medintz IL (2017) Analyzing DNA nanotechnology: a call to arms for the analytical chemistry community. Anal Chem 89(5):2646–2663

  176. 176.

    Amir Y, Ben-Ishay E, Levner D, Ittah S, Abu-Horowitz A, Bachelet I (2014) Universal computing by DNA origami robots in a living animal. Nat Nanotechnol 9(5):353–357

  177. 177.

    Peng R, Zheng X, Lyu Y, Xu L, Zhang X, Ke G, Liu Q, You C, Huan S, Tan W (2018) Engineering a 3D DNA-logic gate nanomachine for bispecific recognition and computing on target cell surfaces. J Am Chem Soc 140(31):9793–9796

Download references

Acknowledgements

This work is supported by the National Natural Science Foundation of China (grants 21705038, 21890744, 21521063, 21605038), the Natural Science Foundation of Hunan Province (2018JJ3029), and Rutgers University.

Author information

Correspondence to Guoliang Ke.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection “DNA Nanotechnology: From Structure to Functionality”; edited by Chunhai Fan, Yonggang Ke.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Fu, X., Peng, F., Lee, J. et al. Aptamer-Functionalized DNA Nanostructures for Biological Applications. Top Curr Chem (Z) 378, 21 (2020). https://doi.org/10.1007/s41061-020-0283-y

Download citation

Keywords

  • Aptamer
  • DNA nanostructures
  • DNA origami
  • Biosensing
  • Bioimaging
  • Drug delivery