Antibody-functionalized polymer-coated gold nanoparticles targeting cancer cells: an in vitro and in vivo study

Gold nanoparticles (∼5 nm) coated with plasma-polymerized allylamine were produced through plasma vapor deposition and bioconjugated with a monoclonal antibody targeting the epidermal growth factor receptor. The resulting nanoconjugates displayed an antibody loading of about 1.7 nmol mg−1 and efficiently target epidermal growth factor receptor overexpressing cell lines, as ascertained by ELISA and Western blot assays. The in vitro targeting properties were also confirmed in vivo, where a similar biodistribution profile of what was experienced for the unconjugated antibody was observed. Thanks to the possibility of doping the gold nanoparticles with radionuclides during plasma vapor deposition, the proposed functionalization strategy represents a very suitable platform for the in vivo cancer targeting with nanosized multifunctional particles.

[1]  S. Curley,et al.  Nanoconjugation modulates the trafficking and mechanism of antibody induced receptor endocytosis , 2010, Proceedings of the National Academy of Sciences.

[2]  Vincent M Rotello,et al.  Gold nanoparticles in delivery applications. , 2008, Advanced drug delivery reviews.

[3]  S. Jelveh,et al.  Gold Nanostructures as a Platform for Combinational Therapy in Future Cancer Therapeutics , 2011, Cancers.

[4]  Naomi J. Halas,et al.  Plasmon Resonance Shifts of Au-Coated Au 2 S Nanoshells: Insight into Multicomponent Nanoparticle Growth , 1997 .

[5]  G. V. van Dongen,et al.  Immuno-PET: a navigator in monoclonal antibody development and applications. , 2007, The oncologist.

[6]  Priyabrata Mukherjee,et al.  Gold nanoparticles: opportunities and challenges in nanomedicine , 2010, Expert opinion on drug delivery.

[7]  Duane E. Prasuhn,et al.  The controlled display of biomolecules on nanoparticles: a challenge suited to bioorthogonal chemistry. , 2011, Bioconjugate chemistry.

[8]  N. Normanno,et al.  Epidermal growth factor receptor (EGFR) signaling in cancer. , 2006, Gene.

[9]  Vincent M Rotello,et al.  Gold nanoparticle-fluorophore complexes: sensitive and discerning "noses" for biosystems sensing. , 2010, Angewandte Chemie.

[10]  Marco Zanella,et al.  Biological applications of gold nanoparticles. , 2008, Chemical Society reviews.

[11]  Younan Xia,et al.  Gold nanostructures: engineering their plasmonic properties for biomedical applications. , 2006, Chemical Society reviews.

[12]  Lev Dykman,et al.  Biodistribution and toxicity of engineered gold nanoparticles: a review of in vitro and in vivo studies. , 2011, Chemical Society reviews.

[13]  Jinatta Jittiwat,et al.  Biodistribution of gold nanoparticles and gene expression changes in the liver and spleen after intravenous administration in rats. , 2010, Biomaterials.

[14]  Xiaohua Huang,et al.  Gold Nanorods: From Synthesis and Properties to Biological and Biomedical Applications , 2009, Advanced materials.

[15]  Junbai Li,et al.  Smart core/shell nanocomposites: intelligent polymers modified gold nanoparticles. , 2009, Advances in colloid and interface science.

[16]  Michael J. Campolongo,et al.  Building plasmonic nanostructures with DNA. , 2011, Nature nanotechnology.

[17]  Xiaohua Huang,et al.  Selective laser photo-thermal therapy of epithelial carcinoma using anti-EGFR antibody conjugated gold nanoparticles. , 2006, Cancer letters.

[18]  M. El-Sayed,et al.  Why gold nanoparticles are more precious than pretty gold: noble metal surface plasmon resonance and its enhancement of the radiative and nonradiative properties of nanocrystals of different shapes. , 2006, Chemical Society reviews.

[19]  Peter W. Stephens,et al.  Nanocrystal gold molecules , 1996 .

[20]  Michele Follen,et al.  Real-time vital optical imaging of precancer using anti-epidermal growth factor receptor antibodies conjugated to gold nanoparticles. , 2003, Cancer research.

[21]  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.

[22]  R. Murray,et al.  Gold nanoelectrodes of varied size: transition to molecule-like charging , 1998, Science.

[23]  Younan Xia,et al.  Gold nanostructures: a class of multifunctional materials for biomedical applications. , 2011, Chemical Society reviews.

[24]  R. Singal,et al.  EGFR targeting of solid tumors. , 2007, Cancer control : journal of the Moffitt Cancer Center.

[25]  K. G. Thomas,et al.  Chromophore-functionalized gold nanoparticles. , 2003, Accounts of chemical research.

[26]  Lisa Brannon-Peppas,et al.  Active targeting schemes for nanoparticle systems in cancer therapeutics. , 2008, Advanced drug delivery reviews.

[27]  Helinor J Johnston,et al.  A review of the in vivo and in vitro toxicity of silver and gold particulates: Particle attributes and biological mechanisms responsible for the observed toxicity , 2010, Critical reviews in toxicology.

[28]  G. Kim,et al.  Targeted Cancer Treatment Using Anti-EGFR and -TFR Antibody-Conjugated Gold Nanoparticles Stimulated by Nonthermal Air Plasma , 2011 .

[29]  Younan Xia,et al.  Shape-Controlled Synthesis of Gold and Silver Nanoparticles , 2002, Science.

[30]  Keishiro Tomoda,et al.  Biodistribution of colloidal gold nanoparticles after intravenous administration: effect of particle size. , 2008, Colloids and surfaces. B, Biointerfaces.

[31]  Manuela Semmler-Behnke,et al.  Particle size-dependent and surface charge-dependent biodistribution of gold nanoparticles after intravenous administration. , 2011, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[32]  Alaaldin M. Alkilany,et al.  Chemical sensing and imaging with metallic nanorods. , 2008, Chemical communications.

[33]  V. Rotello,et al.  Multi-functional gold nanoparticles for drug delivery. , 2007, Advances in experimental medicine and biology.

[34]  Wei Chen,et al.  Sub-nanometre sized metal clusters: from synthetic challenges to the unique property discoveries. , 2012, Chemical Society reviews.

[35]  B. Bay,et al.  Gold nanoparticles in cancer therapy , 2011, Acta Pharmacologica Sinica.

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

[37]  B. Burtness,et al.  Cetuximab: an epidermal growth factor receptor chemeric human-murine monoclonal antibody. , 2005, Drugs of today.

[38]  Younan Xia,et al.  Targeting gold nanocages to cancer cells for photothermal destruction and drug delivery , 2010, Expert opinion on drug delivery.

[39]  O. Feron,et al.  PVD Synthesis and Transfer into Water-Based Solutions of Functionalized Gold Nanoparticles , 2009 .

[40]  J. West,et al.  Antibody-conjugated gold-gold sulfide nanoparticles as multifunctional agents for imaging and therapy of breast cancer , 2010, International journal of nanomedicine.

[41]  Chitta Ranjan Patra,et al.  Fabrication of gold nanoparticles for targeted therapy in pancreatic cancer. , 2010, Advanced drug delivery reviews.

[42]  Rhoderick E. Brown,et al.  Cholesterol Depletion Results in Site-specific Increases in Epidermal Growth Factor Receptor Phosphorylation due to Membrane Level Effects , 2003, Journal of Biological Chemistry.

[43]  D. Astruc,et al.  Applications of vectorized gold nanoparticles to the diagnosis and therapy of cancer. , 2012, Chemical Society reviews.

[44]  Elodie Boisselier,et al.  Gold nanoparticles in nanomedicine: preparations, imaging, diagnostics, therapies and toxicity. , 2009, Chemical Society reviews.

[45]  Heikki Tenhu,et al.  Recent advances in polymer protected gold nanoparticles: synthesis, properties and applications. , 2007, Chemical communications.

[46]  O. Feron,et al.  Antibody immobilization on gold nanoparticles coated layer-by-layer with polyelectrolytes , 2011 .

[47]  P. Jain,et al.  Gold nanoparticles: interesting optical properties and recent applications in cancer diagnostics and therapy. , 2007, Nanomedicine.

[48]  D. Astruc,et al.  Gold nanoparticles: assembly, supramolecular chemistry, quantum-size-related properties, and applications toward biology, catalysis, and nanotechnology. , 2004, Chemical reviews.

[49]  J. Hafner,et al.  Localized surface plasmon resonance sensors. , 2011, Chemical reviews.

[50]  Zhenxin Wang,et al.  Gold nanoparticle probes , 2009 .

[51]  Manuela Semmler-Behnke,et al.  Biodistribution of PEG-modified gold nanoparticles following intratracheal instillation and intravenous injection. , 2010, Biomaterials.

[52]  Dong Liang,et al.  Influence of anchoring ligands and particle size on the colloidal stability and in vivo biodistribution of polyethylene glycol-coated gold nanoparticles in tumor-xenografted mice. , 2009, Biomaterials.