Tailoring of biomimetic high-density lipoprotein nanostructures changes cholesterol binding and efflux.

Gold nanoparticles (Au NPs) were employed as templates to synthesize spherical, high-density lipoprotein (HDL) biomimics (HDL Au NPs) of different sizes and surface chemistries. The effect of size and surface chemistry on the cholesterol binding properties and the ability of the HDL Au NPs to efflux cholesterol from macrophage cells were measured. Results demonstrate that Au NPs may be utilized as templates to generate nanostructures with different physical characteristics that mimic natural HDL. Furthermore, the properties of the HDL Au NPs may be tailored to modulate the ability to bind cholesterol in solution and efflux cholesterol from macrophages. From the conjugates tested, the optimum size and surface chemistry for preparing functional Au NP-templated HDL biomimics were identified.

[1]  J. Storhoff,et al.  A DNA-based method for rationally assembling nanoparticles into macroscopic materials , 1996, Nature.

[2]  G. Zampighi,et al.  Phospholipid vesicle formation and transmembrane protein incorporation using octyl glucoside. , 1981, Biochemistry.

[3]  Chad A Mirkin,et al.  Silver nanoparticle-oligonucleotide conjugates based on DNA with triple cyclic disulfide moieties. , 2007, Nano letters.

[4]  T. Hazlett,et al.  Optical spectroscopy in studies of antibody-hapten interactions. , 2000, Methods.

[5]  S. Nissen,et al.  ETC-216 for coronary artery disease , 2011, Expert opinion on biological therapy.

[6]  A. Jonas Reconstitution of high-density lipoproteins. , 1986, Methods in enzymology.

[7]  A. Jonas,et al.  CHAPTER 17 – Lipoprotein structure , 2008 .

[8]  Christopher K. Glass,et al.  Atherosclerosis The Road Ahead , 2001, Cell.

[9]  Axel Thran,et al.  Atherosclerotic Plaque Composition : Analysis with Multicolor CT and Targeted Gold Nanoparticles 1 , 2010 .

[10]  A. Chattopadhyay Chemistry and biology of N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-labeled lipids: fluorescent probes of biological and model membranes. , 1990, Chemistry and physics of lipids.

[11]  C. Mirkin,et al.  Bioluminescent nanosensors for protease detection based upon gold nanoparticle-luciferase conjugates. , 2010, Chemical communications.

[12]  G. Anantharamaiah,et al.  The amphipathic helix in the exchangeable apolipoproteins: a review of secondary structure and function. , 1992, Journal of lipid research.

[13]  C. Mirkin,et al.  Polyvalent nucleic acid nanostructures. , 2011, Journal of the American Chemical Society.

[14]  L. Curtiss,et al.  Apolipoprotein A-I structural organization in high density lipoproteins isolated from human plasma , 2010, Nature Structural &Molecular Biology.

[15]  Chad A. Mirkin,et al.  Gold nanoparticles for biology and medicine. , 2010, Angewandte Chemie.

[16]  U. Igbavboa,et al.  Lipid binding to sterol carrier protein-2 is inhibited by ethanol. , 1999, Biochimica et biophysica acta.

[17]  Erling Falk,et al.  Pathogenesis of atherosclerosis. , 2006, Journal of the American College of Cardiology.

[18]  A J Mendez,et al.  Cholesterol efflux mediated by apolipoproteins is an active cellular process distinct from efflux mediated by passive diffusion. , 1997, Journal of lipid research.

[19]  Jianwen Fang,et al.  Structure of apolipoprotein A-I in spherical high density lipoproteins of different sizes , 2008, Proceedings of the National Academy of Sciences.

[20]  Zahi A Fayad,et al.  The biological properties of iron oxide core high-density lipoprotein in experimental atherosclerosis. , 2011, Biomaterials.

[21]  J. Storhoff,et al.  Selective colorimetric detection of polynucleotides based on the distance-dependent optical properties of gold nanoparticles. , 1997, Science.

[22]  C. Mirkin,et al.  Templated spherical high density lipoprotein nanoparticles. , 2009, Journal of the American Chemical Society.

[23]  Mathias Brust,et al.  Synthesis of thiol-derivatised gold nanoparticles in a two-phase liquid-liquid system , 1994 .

[24]  Aldons J. Lusis,et al.  Atherosclerosis : Vascular biology , 2000 .

[25]  Z. Fayad,et al.  Quantum dot and Cy5.5 labeled nanoparticles to investigate lipoprotein biointeractions via Förster resonance energy transfer. , 2010, Nano letters.

[26]  R. Lanford,et al.  Signal-mediated nuclear transport in simian virus 40-transformed cells is regulated by large tumor antigen. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[27]  Serkalem Demissie,et al.  Value of High-Density Lipoprotein (HDL) Subpopulations in Predicting Recurrent Cardiovascular Events in the Veterans Affairs HDL Intervention Trial , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[28]  M Sutton,et al.  Polymer-stabilized gold nanoparticles and their incorporation into polymer matrices. , 2001, Journal of the American Chemical Society.

[29]  Paul Schoenhagen,et al.  Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. , 2003, JAMA.

[30]  Elina Ikonen,et al.  Cellular cholesterol trafficking and compartmentalization , 2008, Nature Reviews Molecular Cell Biology.

[31]  D. Vance,et al.  Biochemistry of Lipids, Lipoproteins and Membranes , 2002 .

[32]  D. Rader,et al.  Laboratory assessment of HDL heterogeneity and function. , 2008, Clinical chemistry.

[33]  P. Williams,et al.  Polyacrylamide gradient gel electrophoresis of lipoprotein subclasses. , 2006, Clinics in laboratory medicine.

[34]  Chad A. Mirkin,et al.  Oligonucleotide-Modified Gold Nanoparticles for Intracellular Gene Regulation , 2006, Science.

[35]  Claudia Calcagno,et al.  Nanocrystal core high-density lipoproteins: a multimodality contrast agent platform. , 2008, Nano letters.

[36]  M. K. Brennaman,et al.  Critical flocculation concentrations, binding isotherms, and ligand exchange properties of peptide-modified gold nanoparticles studied by UV-visible, fluorescence, and time-correlated single photon counting spectroscopies. , 2003, Analytical chemistry.

[37]  E. Schaefer,et al.  Metabolic and functional relevance of HDL subspecies , 2011, Current opinion in lipidology.

[38]  D. Astruc,et al.  Gold Nanoparticles: Assembly, Supramolecular Chemistry, Quantum‐Size‐Related Properties, and Applications Toward Biology, Catalysis, and Nanotechnology. , 2004 .

[39]  E. Favari,et al.  Relative Contributions of ABCA1 and SR-BI to Cholesterol Efflux to Serum From Fibroblasts and Macrophages , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[40]  M C Hjortland,et al.  High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. , 1977, The American journal of medicine.

[41]  G. Franceschini,et al.  Synthetic high density lipoproteins for the treatment of myocardial ischemia/reperfusion injury. , 2006, Pharmacology & therapeutics.

[42]  T. B. Thompson,et al.  The Structure of Apolipoprotein A-I in High Density Lipoproteins* , 2007, Journal of Biological Chemistry.

[43]  Y. Marcel,et al.  Apolipoprotein A-I: structure-function relationships. , 2000, Journal of lipid research.

[44]  G. Francis,et al.  Cholesterol and phospholipid efflux from cultured cells. , 2005, Methods.

[45]  Minghan Wang,et al.  HDL: The Metabolism, Function, and Therapeutic Importance , 2004 .

[46]  R. Traut,et al.  Addition of sulfhydryl groups to Escherichia coli ribosomes by protein modification with 2-iminothiolane (methyl 4-mercaptobutyrimidate). , 1978, Biochemistry.

[47]  B. Staels,et al.  Liver X receptor modulators: effects on lipid metabolism and potential use in the treatment of atherosclerosis. , 2009, Biochemical pharmacology.

[48]  L. Margaritis,et al.  Visualisation of liposomes prepared from skin and stratum corneum lipids by transmission electron microscopy. , 2007, Micron.

[49]  C. Mirkin,et al.  Peptide antisense nanoparticles , 2008, Proceedings of the National Academy of Sciences.

[50]  Chad A Mirkin,et al.  Biomimetic high density lipoprotein nanoparticles for nucleic acid delivery. , 2011, Nano letters.

[51]  H. Jiang,et al.  Synthesis of Gold Nanoparticles Grafted with a Thermoresponsive Polymer by Surface-Induced Reversible-Addition-Fragmentation Chain-Transfer Polymerization , 2003 .

[52]  Xiaohua Huang,et al.  Surface plasmon resonance scattering and absorption of anti-EGFR antibody conjugated gold nanoparticles in cancer diagnostics: applications in oral cancer. , 2005, Nano letters.

[53]  C. Mirkin,et al.  Polyvalent oligonucleotide iron oxide nanoparticle "click" conjugates. , 2010, Nano letters.

[54]  Peter Libby,et al.  Lipoprotein Disorders and Cardiovascular Disease , 2012 .

[55]  Inder Singh,et al.  High-density lipoprotein as a therapeutic target: a systematic review. , 2007, JAMA.

[56]  L. Cupples,et al.  High-Density Lipoprotein Subpopulation Profile and Coronary Heart Disease Prevalence in Male Participants of the Framingham Offspring Study , 2004, Arteriosclerosis, thrombosis, and vascular biology.