Skip to main content

DNA Nanoclews for Stimuli-Responsive Anticancer Drug Delivery

  • Chapter
  • First Online:
Rolling Circle Amplification (RCA)
  • 1063 Accesses

Abstract

The technique of rolling circle amplification (RCA) emerged recently as a robust tool to generate the regularly patterned DNA structures in addition to its long-recognized ability of amplifying biological signals. Here, we demonstrate the strategy of RCA-driven generation of nano-scaled cocoon-like DNA particles, designated as DNA nanoclews, for loading and delivering a small molecule anticancer drug. The characteristic biodegradability of DNA was harnessed to control the timing and location of drug release by utilizing a polymeric nanogel encapsulating DNA-degrading enzyme DNase I. This smart drug delivery system based on RCA amplicons could get internalized into targeted cells and release the cargo using the endosomal acidity as a trigger.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Andersen ES, Dong M, Nielsen MM, Jahn K, Subramani R, Mamdouh W, Golas MM, Sander B, Stark H, Oliveira CLP et al (2009) Self-assembly of a nanoscale DNA box with a controllable lid. Nature 459:73–76

    Article  CAS  PubMed  Google Scholar 

  • Anderson RD, Veigl ML, Baxter J, Sedwick WD (1991) DNA sequence specificity of doxorubicin-induced mutational damage in uvrB- Escherichia coli. Cancer Res 51:3930–3937

    CAS  PubMed  Google Scholar 

  • Chen C, Ke J, Zhou XE, Yi W, Brunzelle JS, Li J, Yong E-L, Xu HE, Melcher K (2013) Structural basis for molecular recognition of folic acid by folate receptors. Nature 500:486–489

    Article  CAS  PubMed  Google Scholar 

  • Douglas SM, Marblestone AH, Teerapittayanon S, Vazquez A, Church GM, Shih WM (2009) Rapid prototyping of 3D DNA-origami shapes with caDNAno. Nucleic Acids Res 37:5001–5006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Douglas SM, Bachelet I, Church GM (2012) A logic-gated nanorobot for targeted transport of molecular payloads. Science 335:831–834

    Article  CAS  PubMed  Google Scholar 

  • DuVernay VH, Pachter JA, Crooke ST (1979) Deoxyribonucleic acid binding studies on several new anthracycline antitumor antibiotics. Sequence preference and structure-activity relationships of marcellomycin and its analogs as compared to adriamycin. Biochemistry 18:4024–4030

    Article  CAS  PubMed  Google Scholar 

  • Gu Z, Biswas A, Zhao M, Tang Y (2011) Tailoring nanocarriers for intracellular protein delivery. Chem Soc Rev 40:3638–3655

    Article  CAS  PubMed  Google Scholar 

  • Guo X, Huang L (2012) Recent advances in nonviral vectors for gene delivery. Acc Chem Res 45:971–979

    Article  CAS  PubMed  Google Scholar 

  • 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 53:5821–5826

    Article  CAS  Google Scholar 

  • Jang M, Kim JH, Nam HY, Kwon IC, Ahn HJ (2015) Design of a platform technology for systemic delivery of siRNA to tumours using rolling circle transcription. Nat Commun 6:7930

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee H, Lytton-Jean AKR, Chen Y, Love KT, Park AI, Karagiannis ED, Sehgal A, Querbes W, Zurenko CS, Jayaraman M et al (2012a) Molecularly self-assembled nucleic acid nanoparticles for targeted in vivo siRNA delivery. Nat Nanotechnol 7:389–393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee JB, Hong J, Bonner DK, Poon Z, Hammond PT (2012b) Self-assembled RNA interference microsponges for efficient siRNA delivery. Nat Mater 11:316–322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee K, Rafi M, Wang X, Aran K, Feng X, Lo Sterzo C, Tang R, Lingampalli N, Kim HJ, Murthy N (2015) In vivo delivery of transcription factors with multifunctional oligonucleotides. Nat Mater 14:701–706

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu Y, Sun W, Gu Z (2014) Stimuli-responsive nanomaterials for therapeutic protein delivery. J Control Release 194:1–19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mo R, Jiang T, DiSanto R, Tai W, Gu Z (2014a) ATP-triggered anticancer drug delivery. Nat Commun 5:3364

    Article  CAS  PubMed  Google Scholar 

  • Mo R, Jiang T, Gu Z (2014b) Enhanced anticancer efficacy by ATP-mediated liposomal drug delivery. Angew Chem Int Ed 53:5815–5820

    Article  CAS  Google Scholar 

  • Mo R, Jiang T, Sun W, Gu Z (2015) ATP-responsive DNA-graphene hybrid nanoaggregates for anticancer drug delivery. Biomaterials 50:67–74

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mura S, Nicolas J, Couvreur P (2013) Stimuli-responsive nanocarriers for drug delivery. Nat Mater 12:991–1003

    Article  CAS  PubMed  Google Scholar 

  • Pacardo DB, Ligler FS, Gu Z (2015) Programmable nanomedicine: synergistic and sequential drug delivery systems. Nanoscale 7:3381–3391

    Article  CAS  PubMed  Google Scholar 

  • Roh YH, Lee JB, Shopsowitz KE, Dreaden EC, Morton SW, Poon Z, Hong J, Yamin I, Bonner DK, Hammond PT (2014) Layer-by-layer assembled anti-sense DNA microsponge particles for efficient delivery of cancer therapeutics. ACS Nano 8:9767–9780

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun W, Gu Z (2015) Engineering DNA scaffolds for delivery of anticancer therapeutics. Biomater Sci 3:1018–1024

    Article  CAS  PubMed  Google Scholar 

  • Sun W, Jiang T, Lu Y, Reiff M, Mo R, Gu Z (2014) Cocoon-like self-degradable DNA nanoclew for anticancer drug delivery. J Am Chem Soc 136:14722–14725

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun W, Ji W, Hall JM, Hu Q, Wang C, Beisel CL, Gu Z (2015a) Self-assembled DNA nanoclews for the efficient delivery of CRISPR–Cas9 for genome editing. Angew Chem Int Ed Engl 54(41):12029–12033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun W, Lu Y, Gu Z (2015b) Rolling circle replication for engineering drug delivery carriers. Ther Deliv 6:765–768

    Article  CAS  PubMed  Google Scholar 

  • Udomprasert A, Bongiovanni MN, Sha R, Sherman WB, Wang T, Arora PS, Canary JW, Gras SL, Seeman NC (2014) Amyloid fibrils nucleated and organized by DNA origami constructions. Nat Nanotechnol 9:537–541

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang K, You M, Chen Y, Han D, Zhu Z, Huang J, Williams K, Yang CJ, Tan W (2011) Self-assembly of a bifunctional DNA carrier for drug delivery. Angew Chem Int Ed 50:6098–6101

    Article  CAS  Google Scholar 

  • Wu Y, Sefah K, Liu H, Wang R, Tan W (2010) DNA aptamer–micelle as an efficient detection/delivery vehicle toward cancer cells. Proc Natl Acad Sci U S A 107:5–10

    Article  CAS  PubMed  Google Scholar 

  • Zhao Y-X, Shaw A, Zeng X, Benson E, Nyström AM, Högberg B (2012) DNA origami delivery system for cancer therapy with tunable release properties. ACS Nano 6:8684–8691

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the grant from NC TraCS, NIH’s Clinical and Translational Science Awards (CTSA, 1UL1TR001111) at UNC-CH, the NC State Faculty Research and Professional Development Award, and the start-up package from the Joint BME Department of UNC-CH and NCSU to Z.G.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Wujin Sun or Zhen Gu Ph.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Sun, W., Gu, Z. (2016). DNA Nanoclews for Stimuli-Responsive Anticancer Drug Delivery. In: Demidov, V. (eds) Rolling Circle Amplification (RCA). Springer, Cham. https://doi.org/10.1007/978-3-319-42226-8_12

Download citation

Publish with us

Policies and ethics