Journal Home > Volume 8 , Issue 7

3D DNA origami holds tremendous potential for the encapsulation and selective release of therapeutic drugs. Observations of the real-time performance of these structures in physiological environments will contribute to the development of future applications. We investigated the degradation kinetics of 3D DNA box origami in serum by using high-speed atomic force microscope optimized for imaging 3D DNA origami in real time. The time resolution allowed to characterize the stages of serum effects on individual 3D DNA boxes origami with nanometer resolution. Our results indicate that the digestion process is a combination of rapid collapse and slow degradation phases. Damage to box origami occurs mainly in the collapse phase. Thus, the structural stability of 3D DNA box origami should be improved, especially in the collapse phase, before these structures are used in clinical applications.


menu
Abstract
Full text
Outline
Electronic supplementary material
About this article

Serum-induced degradation of 3D DNA box origami observed with high-speed atomic force microscopy

Show Author's information Zaixing Jiang1,2,§Shuai Zhang2,§Chuanxu Yang2Jørgen Kjems2Yudong Huang1( )Flemming Besenbacher2Mingdong Dong2( )
Department of Polymer Science and TechnologySchool of Chemical Engineering and TechnologyHarbin Institute of TechnologyHarbin150001China
Interdisciplinary Nanoscience Center (iNANO)Aarhus University, DK-8000, Aarhus CDenmark

§These authors contributed equally to this study.

Abstract

3D DNA origami holds tremendous potential for the encapsulation and selective release of therapeutic drugs. Observations of the real-time performance of these structures in physiological environments will contribute to the development of future applications. We investigated the degradation kinetics of 3D DNA box origami in serum by using high-speed atomic force microscope optimized for imaging 3D DNA origami in real time. The time resolution allowed to characterize the stages of serum effects on individual 3D DNA boxes origami with nanometer resolution. Our results indicate that the digestion process is a combination of rapid collapse and slow degradation phases. Damage to box origami occurs mainly in the collapse phase. Thus, the structural stability of 3D DNA box origami should be improved, especially in the collapse phase, before these structures are used in clinical applications.

Keywords: stability, kinetics, 3D DNA box origami, high-speed AFM, serum

References(37)

1

Andersen, E. S.; Dong, M. D.; Nielsen, M. M.; Jahn, K.; Lind-Thomsen, A.; Mamdouh, W.; Gothelf, K. V.; Besenbacher, F.; Kjems, J. DNA origami design of dolphin- shaped structures with flexible tails. ACS Nano 2008, 2, 1213-1218.

2

Rothemund, P. W. K. Folding DNA to create nanoscale shapes and patterns. Nature 2006, 440, 297-302.

3

Tørring, T.; Voigt, N. V.; Nangreave, J.; Yan, H.; Gothelf, K. V. DNA origami: A quantum leap for self-assembly of complex structures. Chem. Soc. Rev. 2011, 40, 5636-5646.

4

Tørring, T.; Helmig, S.; Ogilby, P. R.; Gothelf, K. V. Singlet oxygen in DNA nanotechnology. Acc. Chem. Res. 2014, DOI:10.1021/ar500034y.

5

Wei, B.; Dai, M. J.; Yin, P. Complex shapes self-assembled from single-stranded DNA tiles. Nature 2012, 485, 623- 626.

6

Han, D. R.; Pal, S.; Nangreave, J.; Deng, Z. T.; Liu, Y.; Yan, H. DNA origami with complex curvatures in three-dimensional space. Science 2011, 332, 342-346.

7

Ke, Y. G.; Ong, L. L.; Shih, W. M.; Yin, P. Three-dimensional structures self-assembled from DNA bricks. Science 2012, 338, 1177-1183.

8

Steinhauer, C.; Jungmann, R.; Sobey, T. L.; Simmel, F. C.; Tinnefeld, P. DNA origami as a nanoscopic ruler for super- resolution microscopy. Angew. Chem. Int. Ed. 2009, 48, 8870-8873.

9

Deng, Z. T.; Pal, S.; Samanta, A.; Yan, H.; Liu, Y. DNA functionalization of colloidal Ⅱ-VI semiconductor nanowires for multiplex nanoheterostructures. Chem. Sci. 2013, 4, 2234-2240.

10

Maune, H. T.; Han, S. P.; Barish, R. D.; Bockrath, M.; Goddard, W. A.; Rothemund, P. W. K.; Winfree, E. Self- assembly of carbon nanotubes into two-dimensional geometries using DNA origami templates. Nat. Nanotechnol. 2010, 5, 61-66.

11

Subramani, R.; Juul, S.; Rotaru, A.; Andersen, F. F.; Gothelf, K. V.; Mamdouh, W.; Besenbacher, F.; Dong, M. D.; Knudsen, B. R. A novel secondary DNA binding site in human topoisomerase I unravelled by using a 2D DNA origami platform. ACS Nano 2010, 4, 5969-5977.

12

Ke, Y. G.; Sharma, J.; Liu, M. H.; Jahn, K.; Liu, Y.; Yan, H. Scaffolded DNA origami of a DNA tetrahedron molecular container. Nano Lett. 2009, 9, 2445-2447.

13

Zadegan, R. M.; Jepsen, M. D. E.; Thomsen, K. E.; Okholm, A. H.; Schaffert, D. H.; Andersen, E. S.; Birkedal, V.; Kjems, J. Construction of a 4 zeptoliters switchable 3D DNA box origami. ACS Nano 2012, 6, 10050-10053.

14

Hung, A. M.; Micheel, C. M.; Bozano, L. D.; Osterbur, L. W.; Wallraff, G. M.; Cha, J. N. Large-area spatially ordered arrays of gold nanoparticles directed by lithographically confined DNA origami. Nat. Nanotechnol. 2010, 5, 121-126.

15

Andersen, E. S.; Dong, M.; Nielsen, M. M.; Jahn, K.; Subramani, R.; Mamdouh, W.; Golas, M. M.; Sander, B.; Stark, H.; Oliveira, C. L. P.; et al. Self-assembly of a nanoscale DNA box with a controllable lid. Nature 2009, 459, 73-76.

16

Keum, J. -W.; Bermudez, H. Enhanced resistance of DNA nanostructures to enzymatic digestion. Chem. Commun. 2009, DOI:10.1039/b917661f.

17

Walsh, A. S.; Yin, H. F.; Erben, C. M.; Wood, M. J. A.; Turberfield, A. J. DNA cage delivery to mammalian cells. ACS Nano 2011, 5, 5427-5432.

18

Li, J.; Pei, H.; Zhu, B.; Liang, L.; Wei, M.; He, Y.; Chen, N.; Li, D.; Huang, Q.; Fan, C. H. Self-assembled multivalent DNA nanostructures for noninvasive intracellular delivery of immunostimulatory CpG oligonucleotides. ACS Nano 2011, 5, 8783-8789.

19

Fu, J. L.; Yan, H. Controlled drug release by a nanorobot. Nat. Biotech. 2012, 30, 407-408.

20

Schreiber, R.; Kempter, S.; Holler, S.; Schuller, V.; Schiffels, D.; Simmel, S. S.; Nickels, P. C.; Liedl, T. DNA origami-templated growth of arbitrarily shaped metal nanoparticles. Small 2011, 7, 1795-1799.

21

Li, Z.; Liu, M. H.; Wang, L.; Nangreave, J.; Yan, H.; Liu, Y. Molecular behavior of DNA origami in higher-order self-assembly. J. Am. Chem. Soc. 2010, 132, 13545-13552.

22

Helmig, S.; Rotaru, A.; Arian, D.; Kovbasyuk, L.; Arnbjerg, J.; Ogilby, P. R.; Kjems, J.; Mokhir, A.; Besenbacher, F.; Gothelf, K. V. Single molecule atomic force microscopy studies of photosensitized singlet oxygen behavior on a DNA origami template. ACS Nano 2010, 4, 7475-7480.

23

Liu, J. F.; Geng, Y. L.; Pound, E.; Gyawali, S.; Ashton, J. R.; Hickey, J.; Woolley, A. T.; Harb, J. N. Metallization of branched DNA origami for nanoelectronic circuit fabrication. ACS Nano 2011, 5, 2240-2247.

24

Ding, B. Q.; Deng, Z. T.; Yan, H.; Cabrini, S.; Zuckermann, R. N.; Bokor, J. Gold nanoparticle self-similar chain structure organized by DNA origami. J. Am. Chem. Soc. 2010, 132, 3248-3249.

25

Mo, Y. F.; Turner, K. T.; Szlufarska, I. Friction laws at the nanoscale. Nature 2009, 457, 1116-1119.

26

Mei, Q. A.; Wei, X. X.; Su, F. Y.; Liu, Y.; Youngbull, C.; Johnson, R.; Lindsay, S.; Yan, H.; Meldrum, D. Stability of DNA origami nanoarrays in cell lysate. Nano Lett. 2011, 11, 1477-1482.

27

Conway, J. W.; McLaughlin, C. K.; Castor, K. J.; Sleiman, H. DNA nanostructure serum stability: Greater than the sum of its parts. Chem. Commun. 2013, 49, 1172-1174.

28

Song, J.; Zhang, Z.; Zhang, S.; Liu, L.; Li, Q.; Xie, E. Q.; Gothelf, K. V.; Besenbacher, F.; Dong, M. D. Isothermal hybridization kinetics of DNA assembly of two-dimensional DNA origami. Small 2013, 9, 2954-2959.

29

Song, J.; Arbona, J. -M.; Zhang, Z.; Liu, L.; Xie, E. Q.; Elezgaray, J.; Aime, J. -P.; Gothelf, K. V.; Besenbacher, F.; Dong, M. D. Direct visualization of transient thermal response of a DNA origami. J. Am. Chem. Soc. 2012, 134, 9844-9847.

30

Ando, T.; Uchihashi, T.; Fukuma, T. High-speed atomic force microscopy for nano-visualization of dynamic biomolecular processes. Prog. Surf. Sci. 2008, 83, 337-437.

31

Ando, T.; Kodera, N.; Takai, E.; Maruyama, D.; Saito, K.; Toda, A. A high-speed atomic force microscope for studying biological macromolecules. Proc. Natl. Acad. Sci. 2001, 98, 12468-12472.

32

Rajendran, A.; Endo, M.; Hidaka, K.; Sugiyama, H. Direct and real-time observation of rotary movement of a DNA nanomechanical device. J. Am. Chem. Soc. 2013, DOI:10.1021/ja310454k.

33

Endo, M.; Katsuda, Y.; Hidaka, K.; Sugiyama, H. Regulation of DNA methylation using different tensions of double strands constructed in a defined DNA nanostructure. J. Am. Chem. Soc. 2010, 132, 1592-1597.

34

Sannohe, Y.; Endo, M.; Katsuda, Y.; Hidaka, K.; Sugiyama, H. Visualization of dynamic conformational switching of the G-quadruplex in a DNA nanostructure. J. Am. Chem. Soc. 2010, 132, 16311-16313.

35

Rajendran, A.; Endo, M.; Hidaka, K.; Sugiyama, H. Direct and real-time observation of rotary movement of a DNA nanomechanical device. J. Am. Chem. Soc. 2013, 135, 1117- 1123.

36

Fantner, G. E.; Barbero, R. J.; Gray, D. S.; Belcher, A. M. Kinetics of antimicrobial peptide activity measured on individual bacterial cells using high-speed atomic force microscopy. Nat. Nanotechnol. 2010, 5, 280-285.

37

Andersen, E. S.; Dong, M.; Nielsen, M. M.; Jahn, K.; Subramani, R.; Mamdouh, W.; Golas, M. M.; Sander, B.; Stark, H.; Oliveira, C. L. P.; et al. Self-assembly of a nanoscale DNA box with a controllable lid. Nature 2009, 459, 73-76.

File
12274_2015_724_MOESM1_ESM.pdf (1.3 MB)
12274_2015_724_MOESM2_ESM.wmv (599.4 KB)
12274_2015_724_MOESM3_ESM.wmv (890.4 KB)
12274_2015_724_MOESM5_ESM.wmv (692.5 KB)
12274_2015_724_MOESM4_ESM.wmv (1.1 MB)
12274_2015_724_MOESM6_ESM.wmv (354.9 KB)
12274_2015_724_MOESM7_ESM.wmv (308.4 KB)
Publication history
Copyright
Acknowledgements

Publication history

Received: 07 December 2014
Revised: 09 January 2015
Accepted: 12 January 2015
Published: 11 June 2015
Issue date: July 2015

Copyright

© Tsinghua University Press and Springer‐Verlag Berlin Heidelberg 2015

Acknowledgements

Acknowledgements

The authors acknowledge financial support from CDNA Centre through the Danish National Research Foundation and the financial support from iNANO Center through the Danish Research Agency, the Carlsberg Foundation, and the Villum Foundation. The authors would like to thank UTC Exploration Project (CASC-HIT12-1C03), Opening Project of Key Laboratory of Solid Waste Treatment and Resource Recycle, Ministry of Education (No. 12zxgkI0) and Harbin city science and technology projects (No. 2013DB4BP031).

Return