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Properties of Nucleic Acid Amphiphiles and Their Biomedical Applications

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Aptamers Selected by Cell-SELEX for Theranostics

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Abstract

Nucleic acid-based amphiphiles, which consist of nucleic acids covalently linked to lipophilic lipid molecules, have demonstrated unique physicochemical and biological properties and are emerging as new types of materials in biomedical applications. These types of hybrid materials combine the functions and properties from both hydrophilic nucleic acids and hydrophobic lipid tails and thus are developed to carry therapeutic drugs, to penetrate cell membranes, to decorate the cell surface, and to interact with endogenous proteins. These functional amphiphiles have demonstrated potentials in extending the usage of traditional nucleic acids. In this chapter, we highlight the recent advances with an emphasis on their synthesis, self-assemble properties, and biomedical applications. Specifically, we focus on illustrating the structure–function relationship which provides the foundation for rational design of nucleic acid amphiphiles in future applications in the biomedical field.

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References

  1. Kutzler MA, Weiner DB (2008) DNA vaccines: ready for prime time? Nat Rev Genet 9:776–788

    Article  CAS  Google Scholar 

  2. Okamura K, Lai EC (2008) Endogenous small interfering RNAs in animals. Nat Rev Mol Cell Biol 9:673–678

    Article  CAS  Google Scholar 

  3. Crooke ST (2004) Progress in antisense technology. Annu Rev Med 55:61–95

    Article  CAS  Google Scholar 

  4. Wang K, Tang Z et al (2004) Molecular engineering of DNA: molecular beacons. Angew Chem Int Ed 48:856–870

    Article  Google Scholar 

  5. Keefe AD, Pai S, Ellington A (2010) Aptamers as therapeutics. Nat Rev Drug Discov 9:537–550

    Google Scholar 

  6. Achenbach JC, Chiuman W, Cruz RP, Li Y (2004) DNAzymes: from creation in vitro to application in vivo. Curr Pharm Biotechnol 5:321–336

    Article  CAS  Google Scholar 

  7. Whitehead KA, Langer R (2009) Anderson DG knocking down barriers: advances in siRNA delivery. Nat Rev Drug Discov 8:129–138

    Article  CAS  Google Scholar 

  8. Letsinger RL, Zhang G, Sun DK, Ikeuchi T, Sarin PT (1989) Cholesteryl conjugated oligonucleotides: synthesis, properties, and activity as inhibitors of replication of human immunodeficiency virus in cell culture. Proc Natl Acad Sci USA 86:6553–6556

    Article  CAS  Google Scholar 

  9. Bijsterbosch MK, Rump ET, De Vrueh RL, Dorland RR, Veghel R, Tivell KL, Biessen EA, Berkel TJ, Manoharan M (2000) Modulation of plasma protein binding and in vivo live cell uptake of phosphorothioate oligodeoxynucleotides by cholesterol conjugation. Nucleic Acids Res 28:2717–2725

    Article  CAS  Google Scholar 

  10. Wu Y, Sefan K, Liu H et al (2010) DNA aptamer-micelle as an efficient detection/delivery vehicle toward cancer cells. PNAS 107:5–10

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  12. Ke G, Zhu Z, Wang W et al (2014) A cell-surface-anchored ratiometric fluorescent probe for extracellular pH sensing. ACS Appl Mater Interfaces 6:15329–15334

    CAS  Google Scholar 

  13. Qiu L, Zhang T, Jiang J et al (2014) Cell membrane-anchored biosensors for real-time monitoring of cellular microenvironment 136:13090–13093

    CAS  Google Scholar 

  14. Xiong X, Liu H, Zhao Z et al (2013) DNA aptamer-mediated cell targeting. Angew Chem Int Ed Engl 52:1472–1476

    Article  CAS  Google Scholar 

  15. Wolfrum C, Shi S, Jayaprakash KN et al (2007) Mechanisms and optimization of in vivo delivery of lipophilic siRNAs. Nat Biotechnol 25:1149–1157

    Article  CAS  Google Scholar 

  16. Soutschek J, Akinc A, Bramlage B et al (2004) Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature 432:173–178

    Article  CAS  Google Scholar 

  17. Liu H, Moynihan KD, Zheng Y et al (2014) Structure-based programming of lymph-node targeting in molecular vaccines. Nature 507:519–522

    Article  CAS  Google Scholar 

  18. Bhatia D, Li Y, Ganesh KN (1999) Steroid—DNA conjugates: improved triplex formation with 5-amido-(7-deoxycholic acid)-dU incorporated oligonucleotides. Bioorg Med Chem Lett 9:1789–1794

    Article  CAS  Google Scholar 

  19. Liu H, Zhu Z, Kang H et al (2010) DNA-based micelles: synthesis, micellar properties and size-dependent cell permeability. Chem-Eru J 16:3791–3797

    Article  CAS  Google Scholar 

  20. Anaya M, Kwak M, Musser AJ et al (2010) Tunable hydrophobicity in DNA micelles: design, synthesis, and characterization of a new family of DNA amphiphiles. Chem-Eru J 16:12852–12859

    Article  CAS  Google Scholar 

  21. Borisenko GG, Zaitseva MA, Chuvilin AN, Pozmogova GE (2009) DNA modification of live cell surface. Nucleic Acids Res 37:e28

    Article  Google Scholar 

  22. Brush CK (1995) Lipo-phosphoramidites. US Patent 5,420,330

    Google Scholar 

  23. Chan YH, Lenz P, Boxer SG (2007) Kinetics of DNA-mediated docking reactions between vesicles tethered to supported lipid bilayers. Proc Natl Adad Sci USA 104:18913–18918

    Article  CAS  Google Scholar 

  24. Pokholenko O, Gissot A, Vialet B et al (2013) Lipid oligonucleotide conjugates as responsive nanomaterials for drug delivery. J Mater Chem B 1:5329–5331

    Article  CAS  Google Scholar 

  25. Zimmermann J, Kwak M, Musser AJ, Herrmann A (2011) Amphiphilic DNA block copolymer: nucleic acid-polymer hybrid materials for diagnostics and biomedicine. Methods Mol Biol 751:239–266

    Article  CAS  Google Scholar 

  26. http://www.linktech.co.uk/products/modifiers/hydrophobic_group_cholesterol_palmitate_modification

  27. Schade M, Berti D, Huster D et al (2014) Lipophilic nucleic acids—a flexible construction kit for organization and functionalization of surfaces. Adv Colloid Interface Sci 208:235–251

    Article  CAS  Google Scholar 

  28. Gosse C, Boutorine A, Aujard C, Chami M, Kononov A, Cogne-Laage E, Allemand JF, Li J, Jullien L (2004) Micelles of lipid-oligonucleotide conjugates: implications for membrane anchoring and base pairing. J Phys Chem B 108:6485–6497

    Article  CAS  Google Scholar 

  29. Dentinger PM, Simmons BA, Cruz E, Sprague M (2006) DNA-mediated delivery of lipophilic molecules via hybridization to DNA-based vesicular aggregates. Langmuir 22:2935–2937

    Article  CAS  Google Scholar 

  30. Teixeira F, Rigler JP, Vebert-Nardin C (2007) Nucleo-copolymers: oligonucleotide-based amphiphilic diblock copolymers. Chem Comm 1130–1132

    Google Scholar 

  31. Chen T, Wu C, Jimenez E et al (2013) DNA micelle flares for intracellular mRNA imaging and gene therapy. Angew Chem Int Ed 52:2012–2016

    Article  CAS  Google Scholar 

  32. Rattanakiat S, Nishikawa M, Takakura Y (2012) Self-assembling CpG DNA nanoparticles for efficient antigen delivery and immunostimulation. Eur J Pharm Sci 47:352–358

    Article  CAS  Google Scholar 

  33. Cutler JI, Auyeung E, Mirkin CA (2012) Spherical nucleic acids. J Am Chem Soc 134:1376–1391

    Article  CAS  Google Scholar 

  34. Kabanov AV, Vinogradov SV, Ovchareko AV (1990) A new class of antivirals: antisense oligonucleotides combined with a hydrophobic substituent effectively inhibit influenza virus reproduction and synthesis of virus-specific proteins in MDCK cells. FEBS Lett 259:327–330

    Article  CAS  Google Scholar 

  35. Skobridis K, Husken D, Nicklin P, Haner R (2005) Hybridisation and cellular uptake properties of lipophilic oligonucleotide-dendrimer conjugates. ARKIVOC 6:459–469

    Article  Google Scholar 

  36. Li Z, Zhang Y, Fullhart P, Mirkin CA (2004) Reversible and chemically programmable micelle assembly with DNA block-copolymer amphiphiles. Nano Lett 4:1055–1058

    Article  CAS  Google Scholar 

  37. Weber RJ, Liang SI, Selden NS, Desai TA, Gartner ZJ (2014) Efficient targeting of fatty-acid modified oligonucleotides to live cell membranes through step-wise assembly. Biomacromolecules published online 17 Oct 2014

    Google Scholar 

  38. Pfeiffer I, Hook F (2004) Bivalent cholesterol-based coupling of oligonucleotides to lipid membrane assemblies. J Am Chem Soc 126:10224–10225

    Article  CAS  Google Scholar 

  39. Selden NS, Todhunter ME, Jee NY, Liu JS, Broaders KE, Gartner ZJ (2012) Chemically programmed cell adhesion with membrane-anchored oligonucleotides. J Am Chem Soc 134:765–768

    Article  CAS  Google Scholar 

  40. Sefah K, Shangguan D, Xiong X, O’Donoghue MB, Tan W (2010) Development of DNA aptamers using cell-SELEX. Nat Protoc 5:1169–1185

    Article  CAS  Google Scholar 

  41. Shangguan D, Li Y, Tang Z, Cao Z, Chen HW, Mallikaratchy P, Sefah K, Yang CJ, Tan W (2006) Aptamers evolved from live cells as effective molecular probes for cancer study. Proc Natl Adad Sci USA 103:11838–11843

    Article  CAS  Google Scholar 

  42. Tang Z, Shangguan D, Wang K, Shi H, Sefah K, Mallikratchy P, Chen H, Li Y, Tan W (2007) Selection of aptamers for molecular recognition and characterization of cancer cells. Anal Chem 79:4900–4907

    Article  CAS  Google Scholar 

  43. Kammertoens T, Blankenstein T (2013) It’s the peptide-MHC affinity, stupid. Cancer Cell 23:429–431

    Article  CAS  Google Scholar 

  44. Sefah K, Tang Z, Shangguan D, Chen H, Lepez-Colon D, Li Y, Parekh P, Martin J, Meng L, Philips JA, Kim YM, Tan W (2009) Molecular recognition of acute myloid leukemia using aptamers. Leukemia 23:235–244

    Article  CAS  Google Scholar 

  45. Stephan MT, Irvine DJ (2011) Enhancing cell therapies from the outside in: cell surface engineering using synthetic nanomaterials. Nanotoday 6:309–325

    Google Scholar 

  46. Liu J, Cao Z, Lu Y (2009) Functional nucleic acid sensors. Chem Rev 109:1948–1998

    Article  CAS  Google Scholar 

  47. Liu H, Kwong B, Irvine DJ (2011) Membrane anchored immunostimulatory oligonucleotides for in vivo cell modification and localized immunotherapy. Angew Chem Int Ed 50:7052–7055

    Article  CAS  Google Scholar 

  48. Dennis MS, Zhang M, Meng G, Kadhodayan M et al (2002) Albumin binding as a general strategy for improving the pharmacokinetics of proteins. J Biol Chem 227:35035–35043

    Article  Google Scholar 

  49. Roopenian DC, Akilesh S (2007) FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol 7:715–725

    Article  CAS  Google Scholar 

  50. Juliano RL, Ming X, Nakaguwa O (2012) The chemistry and biology of oligonucleotide conjugates. Acc Chem Res 45:1067–1076

    Article  CAS  Google Scholar 

  51. Pal I, Ramsey JD (2011) The role of the lymphatic system in vaccine trafficking and immune response. Adv Drug Deliv Rev 63:909–922

    Article  CAS  Google Scholar 

  52. Tsopelas C, Sutton R (2002) Why certain dyes are useful for localizing the sentinel lymph node. J Nucl Med 43:1377–1382

    CAS  Google Scholar 

  53. Bachmann MF, Jennings GT (2010) Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns. Nat Rev Immunol 10:787–796

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Chemical Engineering and Materials Science, Wayne State University, Detroit, MI, 48202, USA

    Haipeng Liu

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  1. Haipeng Liu
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Correspondence to Haipeng Liu .

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Editors and Affiliations

  1. Department of Chemistry, Hunan University, Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Bio-Sensing and Chemometrics College of Chemistry and Chemical Engineering, Changsha, China & University of Florida, Gainesville, Florida, USA

    Weihong Tan

  2. Institute of Chemistry, Chinese Academy of Sciences, Beijing, China

    Xiaohong Fang

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Liu, H. (2015). Properties of Nucleic Acid Amphiphiles and Their Biomedical Applications. In: Tan, W., Fang, X. (eds) Aptamers Selected by Cell-SELEX for Theranostics. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-46226-3_7

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