DNA-capped Gold Nanoparticles Research Articles

Tailored Nucleic Acid Architectures at Gold Surfaces for Controlled Therapeutic Release

Nucleic acids are versatile materials capable of forming smart nanocarriers with highly controllable therapeutic delivery. DNA-gated release is a mechanism by which DNA oligonucleotides physically block the release of encapsulated drugs from porous nanoparticles. We extend this mechanism to be used with drugs bound to the surface of DNA-capped gold nanoparticles (AuNPs). We investigated DNA monolayers of different thicknesses and hybridization states to determine how DNA surface architecture can affect the release of a template drug bound to the gold surface. DNA layers are investigated on the planar gold surface via quartz crystal microbalance with dissipation and on AuNPs via dynamic light scattering. The resultant layer architectures were studied for their effect on the release rate of drugs. We observed that varying DNA architectures on AuNPs result in different release rates of the drug. The rate of drug release can be slowed using either folded or randomly coiled DNA sequences, which act as a physical barrier to diffusion. DNA monolayers with upright orientation release drugs more quickly. When the longer single-stranded DNA is used, the drug release is slowed even further. However, even upright DNA layers provide a barrier to drug diffusion at longer sequence lengths. We hypothesize that it is the architecture of the DNA layer, influenced by the folded or upright orientation of individual DNA molecules, that affects the free diffusion of the drug away from the AuNP surface. This mechanism may improve the biological availability of many surface-bound drugs on solid, DNA-capped nanoparticles.

Plasmon switching of gold nanoparticles through thermo-responsive terminal breathing of surface-grafted DNA in hydrated ionic liquids.

Self-assembly performed in ionic liquids (ILs) as a unique solvent promises distinct functions and applications in sensors, therapeutics, and optoelectronic devices due to the rich interactions between nanoparticle building blocks and ILs. However, the general consideration that common nanoparticles are readily destabilized by counterions in an IL has largely prevented researchers from investigating controlled nanoparticle assembly in IL-based systems. This study explores the assembling behaviour of double-stranded (ds) DNA-functionalized gold nanoparticles (dsDNA-AuNPs) in hydrated ionic liquids. The DNA base pair stacking assembly of dsDNA-AuNPs occurs at a low IL concentration (<5%). However, a moderate ionic liquid concentration (5-40%) can de-hybridize dsDNA and leaves single-stranded (ss) DNA stabilizing the AuNPs. In concentrated ionic liquids (>40%), interestingly, the higher ionic strength leads to the assembly of DNA-AuNPs. The triphasic assembly trend is also generally observed regardless of the type of IL. By down-regulation of DNA's melting temperature with the IL, the assembly of DNA-AuNPs affords robust response to a lower temperature range, promising applications in plasmonic devices and range-tunable temperature sensors.

Three-dimensional nanoparticle assemblies with tunable plasmonics via a layer-by-layer process

Recently, DNA has emerged as a designer material for the controlled assembly of nanoparticles. The unique programmability of Watson-Crick base pairing offers limitless control over assembly via specific interactions. At the same time, reliance on non-specific interactions, such as layer-by-layer (LbL) assembly offers a simple assembly method, albeit with limited control. Here, by assembling DNA-capped gold nanoparticles in a LbL fashion we combine these two approaches and present a simple and robust method to construct large-scale three-dimensional nanoparticle assemblies with readily tunable plasmonics. Through variation of the DNA ligand and the nanoparticle core size the morphology of the three-dimensional nanoparticle assemblies was carefully adjusted. These morphological changes, confirmed using grazing incidence x-ray scattering, enabled the tuning of the plasmonic behavior of the three-dimensional nanoparticle assemblies. The morphology could also be modified in real-time through water vapor induced swelling enabling dynamic tuning of the optical properties. The introduction of the DNA ligand to the LbL assembly method presented here imparted tunability to the process previously inaccessible with other nanoparticle ligands and presents a platform with which to create optically active materials of various compositions.

Assembly Dynamics of Plasmonic DNA-Capped Gold Nanoparticle Monolayers.

The self-assembly of nanoparticles in aqueous solutions promises wide applications but requires the careful balance of many parameters not present in organic solvents. While the presence of long-range electrostatic interactions in aqueous solutions may complicate such assemblies, they provide additional parameters through which to control self-assembly. Here, with DNA-capped gold nanoparticles and through the variation of the ionic strength in aqueous solutions, we explored the influence of electrostatic interactions on the adsorption of negatively charged nanoparticles on a positively charged surface. Specifically, we studied the kinetics of nanoparticle adsorption from solution using the quartz crystal microbalance with dissipation (QCM-D). We also characterized the structure of the adsorbed monolayers employing a combination of grazing incidence small-angle X-ray scattering (GISAXS) and scanning electron microscopy. We discovered that adsorption kinetics and monolayer structure were under the control of the DNA ligand length, solution ionic strength, and salt species. We also precisely fit the kinetics to a modified Langmuir model, which converged to the simple Langmuir model at high ionic strengths of magnesium chloride. We demonstrated that increasing the ionic strength and decreasing the DNA ligand lengths increased the surface coverage while decreasing the nanoparticle-nanoparticle spacing. The DNA-capped nanoparticle system reported here provides a readily applicable platform for controlling nanoparticle self-assembly in aqueous solution. Finally, we employ this tunability to create a system with a tunable plasmonic response. Our kinetics studies of the assembly process and further characterizations undertaken will facilitate the construction of nanoparticle arrays with precise structure, and such control will aid in the design of future plasmonic and optoelectronic devices.

Multifunctional DNA-gold nanoparticles for targeted doxorubicin delivery.

In this report we describe the synthesis, characterization, and cytotoxic properties of DNA-capped gold nanoparticles having attached folic acid (FA), a thermoresponsive polymer (p), and/or poly(ethylene glycol) (PEG) oligomers that could be used to deliver the anticancer drug doxorubicin (DOX) in chemotherapy. The FA-DNA oligomer used in the construction of the delivery vehicle was synthesized through the reaction of the isolated folic acid N-hydroxysuccinimide ester with the amino-DNA and the conjugated DNA product was purified using high performance liquid chromatography (HPLC). This approach ultimately allowed control of the amount of FA attached to the surface of the delivery vehicle. Cytotoxicity studies using SK-N-SH neuroblastoma cells with drug loaded delivery vehicles were carried out using a variety of exposure times (1-48 h) and recovery times (1-72 h), and in order to access the effects of varying amounts of attached FA, in culture media deficient in FA. DOX loaded delivery vehicles having 50% of the DNA strands with attached FA were more cytotoxic than when all of the strands contained FA. Since FA stimulates cell growth, the reduced cytotoxicity of vehicles fully covered with FA suggests that the stimulatory effects of FA can more than compensate for the cytotoxic effects of the drug on the cell population. While attachment of hexa-ethylene glycol PEG(18) to the surface of the delivery vehicle had no effect on cytotoxicity, 100% FA plus the thermoresponsive polymer resulted in IC50 = 0.48 ± 0.01 for an exposure time of 24 h and a recovery time of 1 h, which is an order of magnitude more cytotoxic than free DOX. Confocal microscopic studies using fluorescence detection showed that SK-N-SH neuroblastoma cells exposed to DOX-loaded vehicles have drug accumulation inside the cell and, in the case of vehicles with attached FA and thermoresponsive polymer, the drug appears more concentrated. Since the biological target of DOX is DNA, the latter observation is consistent with the high cytotoxicity of vehicles having both FA and the thermoresponsive polymer. The study highlights the potential of DNA-capped gold nanoparticles as delivery vehicles for doxorubicin in cancer chemotherapy.

DNA-capped nanoparticles designed for doxorubicin drug delivery

The anticancer drug, doxorubicin (DOX), was loaded onto DNA-capped gold nanoparticles (AuNP) designed for specific DOX intercalation. Drug binding was confirmed by monitoring DNA melting temperature, AuNP plasmon resonance maximum, and hydrodynamic radius increase, as a function of [DOX]/[DNA] ratio. The capacity for drug release to target DNA was confirmed.

Nanopatterning self-assembled nanoparticle superlattices by moulding microdroplets

Highly ordered arrays of nanoparticles exhibit many properties that are not found in their disordered counterparts. However, these nanoparticle superlattices usually form in a far-from-equilibrium dewetting process, which precludes the use of conventional patterning methods owing to a lack of control over the local dewetting dynamics. Here, we report a simple yet efficient approach for patterning such superlattices that involves moulding microdroplets containing the nanoparticles and spatially regulating their dewetting process. This approach can provide rational control over the local nucleation and growth of the nanoparticle superlattices. Using DNA-capped gold nanoparticles as a model system, we have patterned nanoparticle superlattices over large areas into a number of versatile structures with high degrees of internal order, including single-particle-width corrals, single-particle-thickness microdiscs and submicrometre-sized 'supra-crystals'. Remarkably, these features could be addressed by micropatterned electrode arrays, suggesting potential applications in bottom-up nanodevices.

Melting transition of directly linked gold nanoparticle DNA assembly

DNA melting and hybridization is a fundamental biological process as well as a crucial step in many modern biotechnology applications. DNA confined on surfaces exhibits a behavior different from that in free solutions. The system of DNA-capped gold nanoparticles exhibits unique phase transitions and represents a new class of complex fluids. Depending on the sequence of the DNA, particles can be linked to each other through direct complementary DNA sequences or via a ‘linker’ DNA, whose sequence is complementary to the sequence attached to the gold nanoparticles. We observed different melting transitions for these two distinct systems.

Impedance Sensing of DNA Binding Drugs Using Gold Substrates Modified with Gold Nanoparticles

Interfacial interactions between immobilized DNA probes and DNA-specific sequence binding drugs were investigated using impedance spectroscopy toward the development of a novel biosensing scheme. The impedance measurements are based on the charge-transfer kinetics of the [Fe(CN)6]3-/4- redox couple. Compared to bare gold surfaces, the immobilization of DNA and then the DNA-drug interaction on electrode surfaces altered the capacitance and the interfacial electron resistance and thus diminished the charge-transfer kinetics by reducing the active area of the electrode or by preventing the redox species from approaching the electrode. Electrochemical deposition of gold nanoparticles on a gold electrode surface showed significant improvement in sensitivity. DNA-capped gold nanoparticles on electrodes act as selective sensing interfaces with tunable sensitivity due to higher amounts of DNA probes and the concentric orientation of the DNA self-assembled monolayer. The specificity of the interactions of two classical minor groove binders, mythramycin, a G-C specific-DNA binding anticancer drug, netropsin, an A-T specific-DNA binding drug and an intercalator, nogalamycin on AT-rich DNA-modified substrate and GC-rich DNA-modified substrate are compared. Using gold nanoparticle-deposited substrates, impedance spectroscopy resulted in a 20-40-fold increase in the detection limit. Arrays of deposited gold nanoparticles on gold electrodes offered a convenient tool to subtly control probe immobilization to ensure suitably adsorbed DNA orientation and accessibility of other binding molecules.

A modified nanosphere lithography for the fabrication of aminosilane/polystyrene nanoring arrays and the subsequent attachment of gold or DNA-capped gold nanoparticles

Download options Please wait... Article information DOI https://doi.org/10.1039/B406997H Article type Paper Submitted 10 May 2004 Accepted 10 Aug 2004 First published 28 Sep 2004 Download Citation J. Mater. Chem., 2004,14, 3488-3494 BibTex EndNote MEDLINE ProCite ReferenceManager RefWorks RIS Permissions Request permissions A modified nanosphere lithography for the fabrication of aminosilane/polystyrene nanoring arrays and the subsequent attachment of gold or DNA-capped gold nanoparticles Y. Wang, S. Han, A. L. Briseno, R. J. G. Sanedrin and F. Zhou, J. Mater. Chem., 2004, 14, 3488 DOI: 10.1039/B406997H To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page. If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given. If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page. Read more about how to correctly acknowledge RSC content. Search articles by author Yue Wang Shubo Han Alejandro L. Briseno Raymond J. G. Sanedrin Feimeng Zhou

Phase transition of DNA-linked gold nanoparticles

Melting and hybridization of DNA-capped gold nanoparticle networks are investigated with optical absorption spectroscopy. Single-stranded, 12-base DNA-capped gold nanoparticles are linked with complementary, single-stranded, 24-base linker DNA to form particle networks. Compared to free DNA, a sharp melting transition is seen in these networked DNA-nanoparticle systems. The sharpness is explained by percolation transition phenomena.