DNA-imprinted polymer nanoparticles with monodispersity and prescribed DNA-strand patterns

Abstract

As colloidal self-assembly increasingly approaches the complexity of natural systems, an ongoing challenge is to generate non-centrosymmetric structures. For example, patchy, Janus or living crystallization particles have significantly advanced the area of polymer assembly. It has remained difficult, however, to devise polymer particles that associate in a directional manner, with controlled valency and recognition motifs. Here, we present a method to transfer DNA patterns from a DNA cage to a polymeric nanoparticle encapsulated inside the cage in three dimensions. The resulting DNA-imprinted particles (DIPs), which are ‘moulded’ on the inside of the DNA cage, consist of a monodisperse crosslinked polymer core with a predetermined pattern of different DNA strands covalently ‘printed’ on their exterior, and further assemble with programmability and directionality. The number, orientation and sequence of DNA strands grafted onto the polymeric core can be controlled during the process, and the strands are addressable independently of each other.

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Figure 1: Design and working principle of patterning process.
Figure 2: Characterization of ‘printed’ particle.
Figure 3: Rebinding experiment of ‘printed’ particle 6x to Cb.
Figure 4: Rebinding experiment to the wrong scaffold and molecular simulation.
Figure 5: Controlled valency of DNA-imprinted particles.
Figure 6: Self-assembly of ‘printed’ particle 6x into dimers and trimers.
Figure 7: Self-assembly of ‘printed’ particle 6x into tetramers.

References

  1. 1

    Seeman, N. C. DNA in a material world. Nature 421, 427–431 (2003).

    PubMed  Google Scholar 

  2. 2

    Aldaye, F. A., Palmer, A. L. & Sleiman, H. F. Assembling materials with DNA as the guide. Science 321, 1795–1799 (2008).

    CAS  PubMed  Google Scholar 

  3. 3

    Seeman, N. C. DNA engineering and its application to nanotechnology. Trends Biotechnol. 17, 437–443 (1999).

    CAS  PubMed  Google Scholar 

  4. 4

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

    CAS  PubMed  Google Scholar 

  5. 5

    Aldaye, F. A. & Sleiman, H. F. Modular access to structurally switchable 3D discrete DNA assemblies. J. Am. Chem. Soc. 129, 13376–13377 (2007).

    CAS  PubMed  Google Scholar 

  6. 6

    He, Y. et al. Hierarchical self-assembly of DNA into symmetric supramolecular polyhedra. Nature 452, 198–201 (2008).

    CAS  PubMed  Google Scholar 

  7. 7

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

    CAS  PubMed  Google Scholar 

  8. 8

    Winfree, E., Liu, F., Wenzler, L. A. & Seeman, N. C. Design and self-assembly of two-dimensional DNA crystals. Nature 394, 539–544 (1998).

    CAS  PubMed  Google Scholar 

  9. 9

    Benson, E. et al. DNA rendering of polyhedral meshes at the nanoscale. Nature 523, 441–444 (2015).

    CAS  PubMed  Google Scholar 

  10. 10

    Douglas, S. M. et al. Self-assembly of DNA into nanoscale three-dimensional shapes. Nature 459, 414–418 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. 11

    Ke, Y. et al. Scaffolded DNA origami of a DNA tetrahedron molecular container. Nano Lett. 9, 2445–2447 (2009).

    CAS  PubMed  Google Scholar 

  12. 12

    Kwak, M. & Herrmann, A. Nucleic acid/organic polymer hybrid materials: synthesis, superstructures, and applications. Angew. Chem. Int. Ed. 49, 8574–8587 (2010).

    CAS  Google Scholar 

  13. 13

    Alemdaroglu, F. E. & Herrmann, A. DNA meets synthetic polymers—highly versatile hybrid materials. Org. Biomol. Chem. 5, 1311–1320 (2007).

    CAS  PubMed  Google Scholar 

  14. 14

    Yang, C. J., Pinto, M., Schanze, K. & Tan, W. Direct synthesis of an oligonucleotide–poly(phenylene ethynylene) conjugate with a precise one-to-one molecular ratio. Angew. Chem. Int. Ed. 117, 2628–2632 (2005).

    Google Scholar 

  15. 15

    Jeong, J. H. & Park, T. G. Novel polymer−DNA hybrid polymeric micelles composed of hydrophobic poly(D,L-lactic-co-glycolic acid) and hydrophilic oligonucleotides. Bioconj. Chem. 12, 917–923 (2001).

    CAS  Google Scholar 

  16. 16

    Tan, X. et al. Light-triggered, self-immolative nucleic acid–drug nanostructures. J. Am. Chem. Soc. 137, 6112–6115 (2015).

    CAS  PubMed  Google Scholar 

  17. 17

    Kwak, M. & Herrmann, A. Nucleic acid amphiphiles: synthesis and self-assembled nanostructures. Chem. Soc. Rev. 40, 5745–5755 (2011).

    CAS  PubMed  Google Scholar 

  18. 18

    Edwardson, T. G. W., Carneiro, K. M. M., Serpell, C. J. & Sleiman, H. F. An efficient and modular route to sequence-defined polymers appended to DNA. Angew. Chem. Int. Ed. 53, 4567–4571 (2014).

    CAS  Google Scholar 

  19. 19

    Albert, S. K. et al. Self-assembly of DNA–oligo(p-phenylene-ethynylene) hybrid amphiphiles into surface-engineered vesicles with enhanced emission. Angew. Chem. Int. Ed. 53, 8352–8357 (2014).

    CAS  Google Scholar 

  20. 20

    Jiang, S. et al. Janus particle synthesis and assembly. Adv. Mater. 22, 1060–1071 (2010).

    CAS  PubMed  Google Scholar 

  21. 21

    Wurm, F. & Kilbinger, A. F. M. Polymeric Janus particles. Angew. Chem. Int. Ed. 48, 8412–8421 (2009).

    CAS  Google Scholar 

  22. 22

    Roh, K.-H., Martin, D. C. & Lahann, J. Biphasic Janus particles with nanoscale anisotropy. Nat. Mater. 4, 759–763 (2005).

    CAS  PubMed  Google Scholar 

  23. 23

    Badi, N. & Lutz, J.-F. Sequence control in polymer synthesis. Chem. Soc. Rev. 38, 3383–3390 (2009).

    CAS  PubMed  Google Scholar 

  24. 24

    Lutz, J.-F., Ouchi, M., Liu, D. R. & Sawamoto, M. Sequence-controlled polymers. Science 341, 1238149 (2013).

    PubMed  Google Scholar 

  25. 25

    Qiu, H. et al. Uniform patchy and hollow rectangular platelet micelles from crystallizable polymer blends. Science 352, 697–701 (2016).

    CAS  PubMed  Google Scholar 

  26. 26

    Walther, A. & Müller, A. H. E. Janus particles: synthesis, self-assembly, physical properties, and applications. Chem. Rev. 113, 5194–5261 (2013).

    CAS  PubMed  Google Scholar 

  27. 27

    Suzuki, K., Hosokawa, K. & Maeda, M. Controlling the number and positions of oligonucleotides on gold nanoparticle surfaces. J. Am. Chem. Soc. 131, 7518–7519 (2009).

    CAS  PubMed  Google Scholar 

  28. 28

    Kim, J.-W., Kim, J.-H. & Deaton, R. DNA-linked nanoparticle building blocks for programmable matter. Angew. Chem. Int. Ed. 50, 9185–9190 (2011).

    CAS  Google Scholar 

  29. 29

    Zanchet, D., Micheel, C. M., Parak, W. J., Gerion, D. & Alivisatos, A. P. Electrophoretic isolation of discrete Au nanocrystal/DNA conjugates. Nano Lett. 1, 32–35 (2001).

    CAS  Google Scholar 

  30. 30

    Zhao, Z., Jacovetty, E. L., Liu, Y. & Yan, H. Encapsulation of gold nanoparticles in a DNA origami cage. Angew. Chem. Int. Ed. 50, 2041–2044 (2011).

    CAS  Google Scholar 

  31. 31

    Li, Y., Liu, Z., Yu, G., Jiang, W. & Mao, C. Self-assembly of molecule-like nanoparticle clusters directed by DNA nanocages. J. Am. Chem. Soc. 137, 4320–4323 (2015).

    CAS  PubMed  Google Scholar 

  32. 32

    Wang, Y. et al. Colloids with valence and specific directional bonding. Nature 491, 51–55 (2012).

    CAS  PubMed  Google Scholar 

  33. 33

    Xu, X., Rosi, N. L., Wang, Y., Huo, F. & Mirkin, C. A. Asymmetric functionalization of gold nanoparticles with oligonucleotides. J. Am. Chem. Soc. 128, 9286–9287 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. 34

    Li, Z. et al. Improving the yield of mono-DNA-functionalized gold nanoparticles through dual steric hindrance. J. Am. Chem. Soc. 133, 15284–15287 (2011).

    CAS  PubMed  Google Scholar 

  35. 35

    Pei, H. et al. Designed diblock oligonucleotide for the synthesis of spatially isolated and highly hybridizable functionalization of DNA–gold nanoparticle nanoconjugates. J. Am. Chem. Soc. 134, 11876–11879 (2012).

    CAS  PubMed  Google Scholar 

  36. 36

    Tan, S. J., Campolongo, M. J., Luo, D. & Cheng, W. Building plasmonic nanostructures with DNA. Nat. Nanotech. 6, 268–276 (2011).

    CAS  Google Scholar 

  37. 37

    Maye, M. M., Nykypanchuk, D., Cuisinier, M., van der Lelie, D. & Gang, O. Stepwise surface encoding for high-throughput assembly of nanoclusters. Nat. Mater. 8, 388–391 (2009).

    CAS  PubMed  Google Scholar 

  38. 38

    Tan, L. H., Xing, H., Chen, H. & Lu, Y. Facile and efficient preparation of anisotropic DNA-functionalized gold nanoparticles and their regioselective assembly. J. Am. Chem. Soc. 135, 17675–17678 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. 39

    Tian, Y. et al. Prescribed nanoparticle cluster architectures and low-dimensional arrays built using octahedral DNA origami frames. Nat. Nanotech. 10, 637–644 (2015).

    CAS  Google Scholar 

  40. 40

    Schreiber, R., Santiago, I., Ardavan, A. & Turberfield, A. J. Ordering gold nanoparticles with DNA origami nanoflowers. ACS Nano 10, 7303–7306 (2016).

    CAS  PubMed  Google Scholar 

  41. 41

    Liu, W., Halverson, J., Tian, Y., Tkachenko, A. V. & Gang, O. Self-organized architectures from assorted DNA-framed nanoparticles. Nat. Chem. 8, 867–873 (2016).

    CAS  PubMed  Google Scholar 

  42. 42

    Edwardson, T. G. W., Lau, K. L., Bousmail, D., Serpell, C. J. & Sleiman, H. F. Transfer of molecular recognition information from DNA nanostructures to gold nanoparticles. Nat. Chem. 8, 162–170 (2016).

    CAS  PubMed  Google Scholar 

  43. 43

    Zhang, Y. et al. Transfer of two-dimensional oligonucleotide patterns onto stereocontrolled plasmonic nanostructures through DNA-origami-based nanoimprinting lithography. Angew. Chem. Int. Ed. 55, 8036–8040 (2016).

    CAS  Google Scholar 

  44. 44

    Edwardson, T. G. W., Carneiro, K. M. M., McLaughlin, C. K., Serpell, C. J. & Sleiman, H. F. Site-specific positioning of dendritic alkyl chains on DNA cages enables their geometry-dependent self-assembly. Nat. Chem. 5, 868–875 (2013).

    CAS  PubMed  Google Scholar 

  45. 45

    Serpell, C. J., Edwardson, T. G. W., Chidchob, P., Carneiro, K. M. M. & Sleiman, H. F. Precision polymers and 3D DNA nanostructures: emergent assemblies from new parameter space. J. Am. Chem. Soc. 136, 15767–15774 (2014).

    CAS  PubMed  Google Scholar 

  46. 46

    Chidchob, P., Edwardson, T. G. W., Serpell, C. J. & Sleiman, H. F. Synergy of two assembly languages in DNA nanostructures: self-assembly of sequence-defined polymers on DNA cages. J. Am. Chem. Soc. 138, 4416–4425 (2016).

    CAS  PubMed  Google Scholar 

  47. 47

    Trinh, T., Chidchob, P., Bazzi, H. S. & Sleiman, H. F. DNA micelles as nanoreactors: efficient DNA functionalization with hydrophobic organic molecules. Chem. Commun. 52, 10914–10917 (2016).

    CAS  Google Scholar 

  48. 48

    Liao, C. et al. Melittin aggregation in aqueous solutions: insight from molecular dynamics simulations. J. Phys. Chem. B 119, 10390–10398 (2015).

    CAS  PubMed  Google Scholar 

  49. 49

    Macfarlane, R. J., O'Brien, M. N., Petrosko, S. H. & Mirkin, C. A. Nucleic acid-modified nanostructures as programmable atom equivalents: forging a new ‘table of elements’. Angew. Chem. Int. Ed. 52, 5688–5698 (2013).

    CAS  Google Scholar 

  50. 50

    Jones, M. R., Seeman, N. C. & Mirkin, C. A. Programmable materials and the nature of the DNA bond. Science 347, 1260901 (2015).

    PubMed  Google Scholar 

  51. 51

    Lee, J. H., Yigit, M. V., Mazumdar, D. & Lu, Y. Molecular diagnostic and drug delivery agents based on aptamer-nanomaterial conjugates. Adv. Drug Deliv. Rev. 62, 592–605 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors acknowledge the Natural Sciences and Engineering Research Council of Canada (NSERC), the Canadian Institutes for Health Research, the Centre for Self-Assembled Chemical Structures (CSACS), the Qatar Research Foundation (project no. NPRP 5-1505-1-250) and the Canada Research Chairs Program for financial support. H.F.S. is a Cottrell Scholar of the Research Corporation.

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H.F.S. and T.T. designed the project. T.T. mainly contributed to the production of experimental results. C.L. and J.L. performed computer modelling molecular dynamics simulations of the cube/DNA-polymer. M.B., H.S.B. and V.T. synthesized the hydrophobic unit and its phosphoramidite derivative. All authors agreed to all the content of the manuscript.

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Correspondence to Hanadi F. Sleiman.

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The authors declare no competing financial interests.

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Trinh, T., Liao, C., Toader, V. et al. DNA-imprinted polymer nanoparticles with monodispersity and prescribed DNA-strand patterns. Nature Chem 10, 184–192 (2018). https://doi.org/10.1038/nchem.2893

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