Manipulation of in vitro angiogenesis using peptide-coated gold nanoparticles.

We demonstrate the deliberate activation or inhibition of invitro angiogenesis using functional peptide coated gold nanoparticles. The peptides, anchored to oligo-ethylene glycol capped gold nanospheres, were designed to selectively interact with cell receptors responsible for activation or inhibition of angiogenesis. The functional particles are shown to influence significantly the extent and morphology of vascular structures, without causing toxicity. Mechanistic studies show that the nanoparticles have the ability to alter the balance between naturally secreted pro- and anti-angiogenic factors, under various biological conditions. Nanoparticle-induced control over angiogenesis opens up new directions in targeted drug delivery and therapy.

[1]  Yihai Cao,et al.  It's hard to keep all things angiogenic in one JAR! , 2011, Vascular cell.

[2]  D. Mukhopadhyay,et al.  Pro‐angiogenic Properties of Europium(III) Hydroxide Nanorods , 2008 .

[3]  T. Pellegrino,et al.  Polymer coated inorganic nanoparticles: tailoring the nanocrystal surface for designing nanoprobes with biological implications. , 2012, Nanoscale.

[4]  O. Fernandez-Capetillo,et al.  Neuropilin-1 regulates attachment in human endothelial cells independently of vascular endothelial growth factor receptor-2. , 2005, Blood.

[5]  S. Nitti,et al.  Exocytosis of peptide functionalized gold nanoparticles in endothelial cells. , 2012, Nanoscale.

[6]  Dorota Bartczak,et al.  Receptor-mediated interactions between colloidal gold nanoparticles and human umbilical vein endothelial cells. , 2011, Small.

[7]  P. Nordlander,et al.  Plasmons in strongly coupled metallic nanostructures. , 2011, Chemical reviews.

[8]  K. Schaumburg,et al.  Thioalkylated tetraethylene glycol: a new ligand for water soluble monolayer protected gold clusters. , 2002, Chemical communications.

[9]  J. H. Kim,et al.  The inhibition of retinal neovascularization by gold nanoparticles via suppression of VEGFR-2 activation. , 2011, Biomaterials.

[10]  Otto L Muskens,et al.  Laser-induced damage and recovery of plasmonically targeted human endothelial cells. , 2011, Nano letters.

[11]  N. Thanh,et al.  Functionalisation of nanoparticles for biomedical applications , 2010 .

[12]  Dorota Bartczak,et al.  Diacetylene-containing ligand as a new capping agent for the preparation of water-soluble colloidal nanoparticles of remarkable stability. , 2010, Langmuir : the ACS journal of surfaces and colloids.

[13]  Zhenda Lu,et al.  Colloidal nanoparticle clusters: functional materials by design. , 2012, Chemical Society reviews.

[14]  Mostafa A. El-Sayed,et al.  The golden age: gold nanoparticles for biomedicine. , 2012, Chemical Society reviews.

[15]  Rachel A. Kudgus,et al.  Intrinsic Therapeutic Applications of Noble Metal Nanoparticles: Past, Present and Future , 2012 .

[16]  P. Carmeliet.  Angiogenesis in health and disease , 2003, Nature Medicine.

[17]  J. Folkman.  Angiogenesis in cancer, vascular, rheumatoid and other disease , 1995, Nature Medicine.

[18]  S. Emelianov,et al.  Multifunctional nanoscale strategies for enhancing and monitoring blood vessel regeneration. , 2012, Nano today.

[19]  Ilya Shmulevich,et al.  Robust quantification of in vitro angiogenesis through image analysis , 2005, IEEE Transactions on Medical Imaging.

[20]  W. Risau,et al.  Mechanisms of angiogenesis , 1997, Nature.

[21]  J. Conde,et al.  Design of multifunctional gold nanoparticles for in vitro and in vivo gene silencing. , 2012, ACS nano.

[22]  Otto L Muskens,et al.  Hyperspectral darkfield microscopy of single hollow gold nanoparticles for biomedical applications. , 2013, Physical chemistry chemical physics : PCCP.

[23]  T. Nann,et al.  On the use of pH titration to quantitatively characterize colloidal nanoparticles. , 2012, Langmuir : the ACS journal of surfaces and colloids.

[24]  G. Neufeld,et al.  Vascular endothelial growth factor (VEGF) and its receptors , 1999, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[25]  Erik C. Dreaden,et al.  The Golden Age: Gold Nanoparticles for Biomedicine , 2012 .

[26]  Joseph W. Nichols,et al.  Odyssey of a cancer nanoparticle: from injection site to site of action. , 2012, Nano today.

[27]  Otto L Muskens,et al.  Interactions of human endothelial cells with gold nanoparticles of different morphologies. , 2012, Small.

[28]  D. Mukhopadhyay,et al.  In vivo toxicity studies of europium hydroxide nanorods in mice. , 2009, Toxicology and applied pharmacology.

[29]  C. Pedone,et al.  Peptide‐based Molecules in Angiogenesis , 2006, Chemical biology & drug design.

[30]  Anthony Atala,et al.  Gold Nanoparticles Inhibit VEGF165-Induced Proliferation of HUVEC Cells , 2004 .

[31]  Forrest M Kievit,et al.  Cancer Nanotheranostics: Improving Imaging and Therapy by Targeted Delivery Across Biological Barriers , 2011, Advanced materials.

[32]  G. Breier,et al.  Mechanisms of Angiogenesis , 2005 .

[33]  Subinoy Rana,et al.  Mechanism of anti-angiogenic property of gold nanoparticles: role of nanoparticle size and surface charge. , 2011, Nanomedicine : nanotechnology, biology, and medicine.

[34]  David Schneider,et al.  A new approach to assess gold nanoparticle uptake by mammalian cells: combining optical dark-field and transmission electron microscopy. , 2012, Small.

[35]  A. M. Goodwin.  In vitro assays of angiogenesis for assessment of angiogenic and anti-angiogenic agents. , 2007, Microvascular research.

[36]  Luis M Liz-Marzán,et al.  Intracellular mapping with SERS-encoded gold nanostars. , 2011, Integrative biology : quantitative biosciences from nano to macro.

[37]  P. Carmeliet,et al.  Angiogenesis in cancer and other diseases , 2000, Nature.

[38]  Dorota Bartczak,et al.  Preparation of peptide-functionalized gold nanoparticles using one pot EDC/sulfo-NHS coupling. , 2011, Langmuir : the ACS journal of surfaces and colloids.

[39]  J. Hillier,et al.  A study of the nucleation and growth processes in the synthesis of colloidal gold , 1951 .

[40]  Ling Wang,et al.  Antiangiogenic Properties of Gold Nanoparticles , 2005, Clinical Cancer Research.

[41]  L. Green,et al.  FUNCTIONALIZATION OF NANOPARTICLES FOR BIOMEDICAL APPLICATIONS , 2010 .

[42]  B. Uzzan,et al.  Cardiovascular toxicity of anti-angiogenic drugs , 2011, Targeted Oncology.

[43]  Shiladitya Sengupta,et al.  Nanotechnology-mediated targeting of tumor angiogenesis , 2011, Vascular cell.

[44]  Priyabrata Mukherjee,et al.  Biological properties of "naked" metal nanoparticles. , 2008, Advanced drug delivery reviews.

[45]  Sanjib Bhattacharyya,et al.  Intrinsic therapeutic applications of noble metal nanoparticles: past, present and future. , 2012, Chemical Society reviews.