Antibody-linked spherical nucleic acids for cellular targeting.

Spherical nucleic acid (SNA) constructs are promising new single entity gene regulation materials capable of both cellular transfection and gene knockdown, but thus far are promiscuous structures, exhibiting excellent genetic but little cellular selectivity. In this communication, we describe a strategy to impart targeting capabilities to these constructs through noncovalent functionalization with a complementary antibody-DNA conjugate. As a proof-of-concept, we designed HER2-targeting SNAs and demonstrated that such structures exhibit cell type selectivity in terms of their uptake, and significantly greater gene knockdown in cells overexpressing the target antigen as compared to the analogous antibody-free and off-target materials.

A Photoconductive, Thiophene-Fullerene Double-Cable Polymer, Nanorod Device.

Gold/double-cable copolymer/gold multisegmented nanorods were prepared electrochemically via a template-based method. These "bulk heterojunction" nanorods showed photoconductivity providing us with a platform to study photoinduced charge separation/transport at the nanointerface and begin to think about the rational design of nanoscale solar cells based on such structures.

Biomedical nanotechnology.

This chapter summarizes the roles of nanomaterials in biomedical applications, focusing on those highlighted in this volume. A brief history of nanoscience and technology and a general introduction to the field are presented. Then, the chemical and physical properties of nanostructures that make them ideal for use in biomedical applications are highlighted. Examples of common applications, including sensing, imaging, and therapeutics, are given. Finally, the challenges associated with translating this field from the research laboratory to the clinic setting, in terms of the larger societal implications, are discussed.

Colloidal gold and silver triangular nanoprisms.

It is now well-known that the size, shape, and composition of nanomaterials can dramatically affect their physical and chemical properties, and that technologies based on nanoscale materials have the potential to revolutionize fields ranging from catalysis to medicine. Among these materials, anisotropic particles are particularly interesting because the decreased symmetry of such particles often leads to new and unusual chemical and physical behavior. Within this class of particles, triangular Au and Ag nanoprisms stand out due to their structure- and environment-dependent optical features, their anisotropic surface energetics, and the emergence of reliable synthetic methods for producing them in bulk quantities with control over their edge lengths and thickness. This Review will describe a variety of solution-based methods for synthesizing Au and Ag triangular prismatic structures, and will address and discuss proposed mechanisms for their formation.

Curvature-induced base pair "slipping" effects in DNA-nanoparticle hybridization.

Experiments are presented that suggest DNA strands chemically immobilized on gold nanoparticle surfaces can engage in two types of hybridization: one that involves complementary strands and normal base pairing interactions and a second one assigned as a "slipping" interaction, which can additionally stabilize the aggregate structures through non-Watson-Crick type base pairing or interactions less complementary than the primary interaction. The curvature of the particles appears to be a major factor that contributes to the formation of these slipping interactions as evidenced by the observation that flat gold triangular nanoprism conjugates of the same sequence do not support them. Finally, these slipping interactions significantly stabilize nanoparticle aggregate structures, leading to large increases in T(m)'s and effective association constants as compared with free DNA and particles that do not have the appropriate sequence to maximize their contribution.

"Three-dimensional hybridization" with polyvalent DNA-gold nanoparticle conjugates.

We have determined the minimum number of base pairings necessary to stabilize DNA-Au NP aggregates as a function of salt concentration for particles between 15 and 150 nm in diameter. Significantly, we find that sequences containing a single base pair interaction are capable of effecting hybridization between 150 nm DNA-Au NPs. While traditional DNA hybridization involves two strands interacting in one dimension (1D, Z), we propose that hybridization in the context of an aggregate of polyvalent DNA-Au NP conjugates occurs in three dimensions (many oligonucleotides oriented perpendicular to the X, Y plane engage in base pairing), making nanoparticle assembly possible with three or fewer base pairings per DNA strand. These studies enabled us to compare the stability of duplex DNA free in solution and bound to the nanoparticle surface. We estimate that 4-8, 6-19, or 8-33 additional DNA bases must be added to free duplex DNA to achieve melting temperatures equivalent to hybridized systems formed from 15, 60, or 150 nm DNA-Au NPs, respectively. In addition, we estimate that the equilibrium binding constant (K(eq)) for 15 nm DNA-Au NPs (3 base pairs) is approximately 3 orders of magnitude higher than the K(eq) for the corresponding nanoparticle free system.

Screening the sequence selectivity of DNA-binding molecules using a gold nanoparticle-based colorimetric approach.

We have developed a novel competition assay that uses a gold nanoparticle (Au NP)-based, high-throughput colorimetric approach to screen the sequence selectivity of DNA-binding molecules. This assay hinges on the observation that the melting behavior of DNA-functionalized Au NP aggregates is sensitive to the concentration of the DNA-binding molecule in solution. When short, oligomeric hairpin DNA sequences were added to a reaction solution consisting of DNA-functionalized Au NP aggregates and DNA-binding molecules, these molecules may either bind to the Au NP aggregate interconnects or the hairpin stems based on their relative affinity for each. This relative affinity can be measured as a change in the melting temperature (Tm) of the DNA-modified Au NP aggregates in solution. As a proof of concept, we evaluated the selectivity of 4',6-diamidino-2-phenylindone (an AT-specific binder), ethidium bromide (a nonspecific binder), and chromomycin A (a GC-specific binder) for six sequences of hairpin DNA having different numbers of AT pairs in a five-base pair variable stem region. Our assay accurately and easily confirmed the known trends in selectivity for the DNA binders in question without the use of complicated instrumentation. This novel assay will be useful in assessing large libraries of potential drug candidates that work by binding DNA to form a drug/DNA complex.

Silver nanoparticle-oligonucleotide conjugates based on DNA with triple cyclic disulfide moieties.

We report a new strategy for preparing silver nanoparticle-oligonucleotide conjugates that are based upon DNA with cyclic disulfide-anchoring groups. These particles are extremely stable and can withstand NaCl concentrations up to 1.0 M. When silver nanoparticles functionalized with complementary sequences are combined, they assemble to form DNA-linked nanoparticle networks. This assembly process is reversible with heating and is associated with a red shifting of the particle surface plasmon resonance and a concomitant color change from yellow to pale red. Analogous to the oligonucleotide-functionalized gold nanoparticles, these particles also exhibit highly cooperative binding properties with extremely sharp melting transitions. This work is an important step toward using silver nanoparticle-oligonucleotide conjugates for a variety of purposes, including molecular diagnostic labels, synthons in programmable materials synthesis approaches, and functional components for nanoelectronic and plasmonic devices.

Maximizing DNA loading on a range of gold nanoparticle sizes.

We have investigated the variables that influence DNA coverage on gold nanoparticles. The effects of salt concentration, spacer composition, nanoparticle size, and degree of sonication have been evaluated. Maximum loading was obtained by salt aging the nanoparticles to approximately 0.7 M NaCl in the presence of DNA containing a poly(ethylene glycol) spacer. In addition, DNA loading was substantially increased by sonicating the nanoparticles during the surface loading process. Last, nanoparticles up to 250 nm in diameter were found have approximately 2 orders of magnitude higher DNA loading than smaller (13-30 nm) nanoparticles, a consequence of their larger surface area. Stable large particles are attractive for a variety of biodiagnostic assays.

Multisegmented one-dimensional nanorods prepared by hard-template synthetic methods.

In the science and engineering communities, the nanoscience revolution is intensifying. As many types of nanomaterials are becoming more reliably synthesized, they are being used for novel applications in all branches of nanoscience and nanotechnology. Since it is sometimes desirable for single nanomaterials to perform multiple functions simultaneously, multicomponent nanomaterials, such as core-shell, alloyed, and striped nanoparticles, are being more extensively researched. Nanoscientists hope to design multicomponent nanostructures and exploit their inherent multiple functionalities for use in many novel applications. This review highlights recent advances in the synthesis of multisegmented one-dimensional nanorods and nanowires with metal, semiconductor, polymer, molecular, and even gapped components. It also discusses the applications of these multicomponent nanomaterials in magnetism, self-assembly, electronics, biology, catalysis, and optics. Particular emphasis is placed on the new materials and devices achievable using these multicomponent, rather than single-component, nanowire structures.