title: Using temperature-sensitive smart polymers to regulate DNA-mediated nanoassembly and encoded nanocarrier drug release.
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.
authors.affiliation: Department of Chemistry, Syracuse University, Syracuse, New York 13244, United States.
authors.forename: Kristen L
authors.initials: KL
authors.lastname: Hamner
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Alexander
authors.forename: Kaitlin
authors.initials: K
authors.lastname: Coopersmith
authors.forename: David
authors.initials: D
authors.lastname: Reishofer
authors.forename: Christina
authors.initials: C
authors.lastname: Provenza
authors.forename: Mathew M
authors.initials: MM
authors.lastname: Maye
mesh_terms: D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry*; D004277:DNA, Single-Stranded / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage*; D004337:Drug Carriers / Q000737:chemistry*; D006046:Gold / Q000737:chemistry; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry*; D009693:Nucleic Acid Hybridization; D011108:Polymers / Q000737:chemistry*; D013696:Temperature; D013997:Time Factors; D014466:Ultraviolet Rays
chemical_list: D004277:DNA, Single-Stranded; D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; D006046:Gold; D004317:Doxorubicin; D004247:DNA