Instantaneous and quantitative functionalization of gold nanoparticles with thiolated DNA using a pH-assisted and surfactant-free route.

The attachment of thiolated DNA to gold nanoparticles (AuNPs) has enabled many landmark works in nanobiotechnology. This conjugate chemistry is typically performed using a salt-aging protocol where, in the presence of an excess amount of DNA, NaCl is gradually added to increase DNA loading over 1-2 days. To functionalize large AuNPs, surfactants need to be used, which may generate difficulties for downstream biological applications. We report herein a novel method using a pH 3.0 citrate buffer to complete the attachment process in a few minutes. More importantly, it allows for quantitative DNA adsorption, eliminating the need to quantify the number of adsorbed DNA and allowing the adsorption of multiple DNAs with different sequences at predetermined ratios. The method has been tested for various DNAs over a wide range of AuNP sizes. Our work suggests a synergistic effect between pH and salt in DNA attachment and reveals the fundamental kinetics of AuNP aggregation versus DNA adsorption, providing a novel means to modulate the interactions between DNA and AuNPs.

[1]  N O Reich,et al.  Nanometal surface energy transfer in optical rulers, breaking the FRET barrier. , 2005, Journal of the American Chemical Society.

[2]  Chad A Mirkin,et al.  The role radius of curvature plays in thiolated oligonucleotide loading on gold nanoparticles. , 2009, ACS nano.

[3]  Julianne M. Gibbs-Davis,et al.  Tuning ratios, densities, and supramolecular spacing in bifunctional DNA-modified gold nanoparticles. , 2012, Small.

[4]  Itamar Willner,et al.  Integrated nanoparticle-biomolecule hybrid systems: synthesis, properties, and applications. , 2004, Angewandte Chemie.

[5]  L. Rothberg,et al.  Kinetics and mechanism of single-stranded DNA adsorption onto citrate-stabilized gold nanoparticles in colloidal solution. , 2011, Langmuir : the ACS journal of surfaces and colloids.

[6]  P. Schultz,et al.  Organization of 'nanocrystal molecules' using DNA , 1996, Nature.

[7]  Juewen Liu,et al.  Preparation of aptamer-linked gold nanoparticle purple aggregates for colorimetric sensing of analytes , 2006, Nature Protocols.

[8]  Ronghua Yang,et al.  Nucleic acid conjugated nanomaterials for enhanced molecular recognition. , 2009, ACS nano.

[9]  Shaojun Dong,et al.  Biomolecule-nanoparticle hybrids for electrochemical biosensors , 2009 .

[10]  N. Seeman.  DNA in a material world , 2003, Nature.

[11]  T. M. Herne,et al.  Characterization of DNA Probes Immobilized on Gold Surfaces , 1997 .

[12]  Chad A Mirkin,et al.  Maximizing DNA loading on a range of gold nanoparticle sizes. , 2006, Analytical chemistry.

[13]  Chad A. Mirkin,et al.  Programmed Materials Synthesis with DNA. , 1999, Chemical reviews.

[14]  Zhiqiang Gao,et al.  Sequence-selective recognition of nucleic acids under extremely low salt conditions using nanoparticle probes. , 2011, Analytical chemistry.

[15]  Subinoy Rana,et al.  Nanoparticles for detection and diagnosis. , 2010, Advanced drug delivery reviews.

[16]  Juewen Liu,et al.  Programmable assembly of DNA-functionalized liposomes by DNA. , 2011, ACS nano.

[17]  Z. Tang,et al.  Design and application of inorganic nanoparticle superstructures: current status and future challenges. , 2011, Small.

[18]  Juewen Liu,et al.  Amplifying the macromolecular crowding effect using nanoparticles. , 2012, Journal of the American Chemical Society.

[19]  Hao Yan,et al.  DNA-directed artificial light-harvesting antenna. , 2011, Journal of the American Chemical Society.

[20]  Po-Jung Jimmy Huang,et al.  DNA-length-dependent fluorescence signaling on graphene oxide surface. , 2012, Small.

[21]  Dongsheng Liu,et al.  Improving the yield of mono-DNA-functionalized gold nanoparticles through dual steric hindrance. , 2011, Journal of the American Chemical Society.

[22]  George C Schatz,et al.  What controls the melting properties of DNA-linked gold nanoparticle assemblies? , 2000, Journal of the American Chemical Society.

[23]  Po-Jung Jimmy Huang,et al.  Dissociation and degradation of thiol-modified DNA on gold nanoparticles in aqueous and organic solvents. , 2011, Langmuir : the ACS journal of surfaces and colloids.

[24]  Chad A. Mirkin,et al.  One-Pot Colorimetric Differentiation of Polynucleotides with Single Base Imperfections Using Gold Nanoparticle Probes , 1998 .

[25]  D. Lelie,et al.  DNA-guided crystallization of colloidal nanoparticles , 2008, Nature.

[26]  Hui Li,et al.  Effect of pH on the Interaction of Gold Nanoparticles with DNA and Application in the Detection of Human p53 Gene Mutation , 2008, Nanoscale research letters.

[27]  Zhiqiang Gao,et al.  Facile and controllable loading of single-stranded DNA on gold nanoparticles. , 2009, Analytical chemistry.

[28]  Hao Yan,et al.  Challenges and opportunities for structural DNA nanotechnology. , 2011, Nature nanotechnology.

[29]  Chunhai Fan,et al.  Target-responsive structural switching for nucleic acid-based sensors. , 2010, Accounts of chemical research.

[30]  M. Dresselhaus,et al.  Structure-Based Carbon Nanotube Sorting by Sequence-Dependent DNA Assembly , 2003, Science.

[31]  Juewen Liu,et al.  Accelerated color change of gold nanoparticles assembled by DNAzymes for simple and fast colorimetric Pb2+ detection. , 2004, Journal of the American Chemical Society.

[32]  Sarah J. Hurst,et al.  "Three-dimensional hybridization" with polyvalent DNA-gold nanoparticle conjugates. , 2008, Journal of the American Chemical Society.

[33]  Hao Yan,et al.  Self-assembled DNA nanostructures for distance-dependent multivalent ligand-protein binding. , 2008, Nature nanotechnology.

[34]  Michael A. Brook,et al.  Design of Gold Nanoparticle‐Based Colorimetric Biosensing Assays , 2008, Chembiochem : a European journal of chemical biology.

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

[36]  Chad A Mirkin,et al.  Nanostructures in biodiagnostics. , 2005, Chemical reviews.

[37]  M. Servos,et al.  Surface science of DNA adsorption onto citrate-capped gold nanoparticles. , 2012, Langmuir : the ACS journal of surfaces and colloids.

[38]  Sung Yong Park,et al.  DNA-programmable nanoparticle crystallization , 2008, Nature.

[39]  T Andrew Taton,et al.  DNA dissociation and degradation at gold nanoparticle surfaces. , 2006, Colloids and surfaces. B, Biointerfaces.

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

[41]  Chad A Mirkin,et al.  Bio-bar-code-based DNA detection with PCR-like sensitivity. , 2004, Journal of the American Chemical Society.

[42]  C. Mirkin,et al.  A fluorescence-based method for determining the surface coverage and hybridization efficiency of thiol-capped oligonucleotides bound to gold thin films and nanoparticles. , 2000, Analytical chemistry.

[43]  Juewen Liu,et al.  Functional nucleic acid sensors. , 2009, Chemical reviews.

[44]  Chad A Mirkin,et al.  Spherical nucleic acids. , 2012, Journal of the American Chemical Society.

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