title: Controlling lipid micelle stability using oligonucleotide headgroups.
abstract: Lipid-based micelles provide an attractive option for therapeutic and diagnostic applications because of their small size (<20 nm) and ability to self-assemble and improve the solubility of both hydrophobic drugs and dyes. Their use, however, has been challenged by the fact that these particles are inherently unstable in serum becaue of interactions with protein components, which drives the micelle equilibrium to the monomeric state. We have engineered serum stabilized micelles using short quadruplex forming oligonucleotide extensions as the lipid headgroup. Quadruplex formation on the surface of the particles, confirmed by (1)H NMR, results in slight distortion of the otherwise spherical micelles and renders them resistant to disassembly by serum proteins for >24 h. Using antisense oligonucleotides we demonstrated that disruption of the quadruplex leads to micelle destabilization and cargo release. The ability to use oligonucleotide interactions to control lipid particle stability represents a new approach in the design of programmed nanoscale devices.
authors: Department of Biochemistry, Albert Einstein College of Medicine , Bronx, New York 10461, United States.
authors: Samantha E
authors: SE
authors: Wilner
authors: Samuel E
authors: SE
authors: Sparks
authors: David
authors: D
authors: Cowburn
authors: Mark E
authors: ME
authors: Girvin
authors: Matthew
authors: M
authors: Levy
mesh_terms: D008055:Lipids / Q000737:chemistry*; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D009841:Oligonucleotides / Q000737:chemistry*
chemical_list: D008055:Lipids; D008823:Micelles; D009841:Oligonucleotides
references: J Control Release. 2001 Jun 15;73(2-3):137-72
references: 11516494
references: Biomaterials. 2011 Sep;32(27):6633-45
references: 21658763
references: J Phys Chem B. 2010 Oct 7;114(39):12632-40
references: 20828210
references: Langmuir. 2008 May 20;24(10):5213-7
references: 18257595
references: Proc Natl Acad Sci U S A. 2008 May 6;105(18):6596-601
references: 18445654
references: Biomacromolecules. 2007 Jul;8(7):2244-9
references: 17585805
references: Biopolymers. 2006 Dec 15;83(6):584-94
references: 16944520
references: J Am Chem Soc. 2005 Dec 7;127(48):16892-9
references: 16316235
references: Biomacromolecules. 2005 Sep-Oct;6(5):2541-54
references: 16153091
references: Langmuir. 2005 Apr 12;21(8):3279-90
references: 15807565
references: Biochemistry. 1999 Apr 6;38(14):4355-64
references: 10194354
references: Biochemistry. 1992 Sep 15;31(36):8406-14
references: 1382577
references: J Am Chem Soc. 2003 Feb 12;125(6):1643-54
references: 12568626
references: Nucleic Acids Res. 2002 Nov 1;30(21):4740-50
references: 12409465
references: ACS Nano. 2012 Jun 26;6(6):5320-9
references: 22545944
references: J Am Chem Soc. 2012 Jul 18;134(28):11807-14
references: 22731391
references: Methods. 2012 May;57(1):11-24
references: 22633887
references: Nat Nanotechnol. 2013 Aug;8(8):580-6
references: 23892986
references: Nat Chem. 2013 Oct;5(10):868-75
references: 24056344
references: Bioconjug Chem. 2012 Jun 20;23(6):1091-104
references: 22372953
references: Nat Nanotechnol. 2014 May;9(5):353-7
references: 24705510
references: J Am Chem Soc. 2014 Aug 13;136(32):11198-211
references: 25029570
references: Science. 2012 Feb 17;335(6070):831-4
references: 22344439
references: J Am Chem Soc. 2012 Jan 18;134(2):765-8
references: 22176556