Using temperature-sensitive smart polymers to regulate DNA-mediated nanoassembly and encoded nanocarrier drug release

Kristen L. Hamner, Colleen M. Alexander, Kaitlin Coopersmith, David Reishofer, Christina Provenza, Mathew M Maye

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

In this paper we describe the use of a temperature-responsive polymer to regulate DNA interactions in both a DNA-mediated assembly system and a DNA-encoded drug delivery system. A thermoresponsive pNIPAAm-co-pAAm polymer, with a transition temperature (TC) of 51 C, was synthesized with thiol modification and grafted onto gold nanoparticles (Au NPs) also containing single-stranded oligonucleotides (ssDNA). The thermoresponsive behavior of the polymer regulated the accessibility of the sequence-specific hybridization between complementary DNA-functionalized Au NPs. At T < TC, the polymer was hydrophilic and extended, blocking interaction between the complementary sequences at the periphery of the hydrodynamic diameter. In contrast, at T > TC, the polymer shell undergoes a hydrophilic to -phobic phase transition and collapses, shrinking below the outer ssDNA, allowing for the sequence-specific hybridization to occur. The potential application of this dynamic interface for drug delivery is shown, in which the chemotherapy drug doxorubicin (DOX) is bound to double-stranded DNA (dsDNA)-functionalized Au NPs whose sequences are known to be high-affinity intercalation points for it. The presence of the polymer capping is shown to decrease drug release kinetics and equilibrium at T < TC, but increase release at T > TC, thus improving the cytotoxicity of the encoded nanocarrier design.

Original languageEnglish (US)
Pages (from-to)7011-7020
Number of pages10
JournalACS Nano
Volume7
Issue number8
DOIs
StatePublished - Aug 27 2013

Fingerprint

Polymers
drugs
Temperature
polymers
Pharmaceutical Preparations
delivery
temperature
Chemotherapy
oligonucleotides
Transition Temperature
Oligonucleotides
Phase Transition
Drug Delivery Systems
chemotherapy
Cytotoxicity
Intercalation
Drug delivery
Sulfhydryl Compounds
thiols
intercalation

Keywords

  • copolymer
  • DNA
  • dynamic
  • nanoparticle
  • responsive
  • self-assembly
  • smart

ASJC Scopus subject areas

  • Engineering(all)
  • Materials Science(all)
  • Physics and Astronomy(all)
  • Medicine(all)

Cite this

Using temperature-sensitive smart polymers to regulate DNA-mediated nanoassembly and encoded nanocarrier drug release. / Hamner, Kristen L.; Alexander, Colleen M.; Coopersmith, Kaitlin; Reishofer, David; Provenza, Christina; Maye, Mathew M.

In: ACS Nano, Vol. 7, No. 8, 27.08.2013, p. 7011-7020.

Research output: Contribution to journalArticle

Hamner, Kristen L. ; Alexander, Colleen M. ; Coopersmith, Kaitlin ; Reishofer, David ; Provenza, Christina ; Maye, Mathew M. / Using temperature-sensitive smart polymers to regulate DNA-mediated nanoassembly and encoded nanocarrier drug release. In: ACS Nano. 2013 ; Vol. 7, No. 8. pp. 7011-7020.
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