Polyvalent DNA Nanoparticle Conjugates Stabilize Nucleic Acids

Seferos, Dwight S.; Prigodich, Andrew E.; Giljohann, David A.; Patel, Pinal C.; Mirkin, Chad A.

doi:10.1021/nl802958f

Cited by 495 publications

(485 citation statements)

References 39 publications

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“…polyvalent nanoconjugate), 11 including cooperative melting transition, tighter binding to complementary DNA, cell internalization, and resistance against nuclease degradation. [17][18][19][20][21] For the second strategy, non-thiolated DNAs can be adsorbed onto AuNPs via the DNA bases.…”

Section: This Document Is the Accepted Manuscript Version Of A Publismentioning

confidence: 99%

Instantaneous Attachment of an Ultrahigh Density of Nonthiolated DNA to Gold Nanoparticles and Its Applications

et al. 2012

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The last 16 years have witnessed the landmark development of polyvalent thiolated DNA functionalized gold nanoparticles (AuNPs) possessing striking properties within the emerging field of nanobiotechnology. Many novel properties of this hybrid nanomaterial are attributed to the dense DNA shell. However, the question of whether non-thiolated polyvalent DNA-AuNP could be fabricated with high DNA density and similar properties as its thiolated counterpart has not been explored in detail.Herein, we report that by simply tuning the pH of the DNA/AuNP mixture, an ultrahigh capacity of nonthiolated DNA can be conjugated to AuNPs in a few minutes, resulting in polyvalent DNA-AuNP conjugates with cooperative melting behavior, a typical property for polyvalent thiolated DNA functionalized AuNPs. With this method, large AuNPs (e.g., 50 nm) can be functionalized to achieve colorimetric detection of sub-nM DNA. Further, this fast and stable DNA loading was employed to separate AuNPs of different size. We propose that a large fraction of the attached DNAs are adsorbed via one or a few terminal bases to afford the high loading capacity and the ability to hybridize with the complementary DNA. This discovery not only offers a time-and cost-effective way to functionalize AuNPs with a high density of non-thiolated DNA, but also provides new insights into the fundamental understanding of how DNA strands with different sequences interact with AuNPs.

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Section: This Document Is the Accepted Manuscript Version Of A Publismentioning

confidence: 99%

Instantaneous Attachment of an Ultrahigh Density of Nonthiolated DNA to Gold Nanoparticles and Its Applications

et al. 2012

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“…[3c] Additionally, the dense layer of oligonucleotides on SNAs makes them resistant to degradation and provides increased stability compared to the linear form. [4] These differences between SNAs and linear nucleic acids highlight the need to understand protein-SNA interactions in complex biological media, ranging from in vitro to in vivo systems. Immediately upon intravenous administration, particles encounter a multitude of serum proteins that often form a corona around the nanoparticle and may significantly alter its in vivo behavior.…”

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confidence: 99%

Spherical Nucleic Acid Nanoparticle Conjugates Enhance G‐Quadruplex Formation and Increase Serum Protein Interactions

2014

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To understand the effect of three-dimensional oligonucleotide structure on protein corona formation, we studied the identity and quantity of human serum proteins that bind to spherical nucleic acid (SNA) nanoparticle conjugates. SNAs exhibit cellular uptake properties that are remarkably different from those of linear nucleic acids, which have been related to their interaction with certain classes of proteins. Through a proteomic analysis, this work shows that the protein binding properties of SNAs are sequence-specific and supports the conclusion that the oligonucleotide tertiary structure can significantly alter the chemical composition of the SNA protein corona. This knowledge will impact our understanding of how nucleic acid-based nanostructures, and SNAs in particular, function in complex biological milieu.

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“…The drastically increased local counterion concentration around DNA-functionalized gold nanoparticles has also been suggested to be responsible for protecting DNA from nuclease degradation by Mirkin and coworkers. 45 Reaction Kinetics. To understand the time-dependent signal change of the immobilized sensor, kinetic studies have been performed by taking aliquots out and analyzing by flow cytometry at designated time points after adding 2 or 10 mM adenosine.…”

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confidence: 99%

Flow Cytometry-Assisted Detection of Adenosine in Serum with an Immobilized Aptamer Sensor

Huang

Liu

2010

Anal. Chem.

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Aptamers are single-stranded nucleic acids that can selectively bind to essentially any molecule of choice. Because of their high stability, low cost, ease of modification and availability through selection, aptamers hold great promise in addressing key challenges in bioanalytical chemistry. In the past fifteen years many highly sensitive fluorescent aptamer sensors have been reported. However, few such sensors showed high performance in serum samples. Further challenges related to practical applications include detection in a very small sample volume and a low dependence of sensor performance on ionic strength.We report the immobilization of an aptamer sensor on a magnetic microparticle and the use of flow cytometry for detection. Flow cytometry allows the detection of individual particles in a capillary and can effectively reduce the light scattering effect of serum. Since DNA immobilization generated a highly negatively charged surface and caused an enrichment of counter ions, the sensor performance showed a lower salt dependence. The detection limits for adenosine are determined to be 178 and 167 M in buffer and in 30% serum, respectively. Finally, we demonstrated that the detection can be carried out in 10 L of 90% human blood serum.3

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Polyvalent DNA Nanoparticle Conjugates Stabilize Nucleic Acids

Cited by 495 publications

References 39 publications

Instantaneous Attachment of an Ultrahigh Density of Nonthiolated DNA to Gold Nanoparticles and Its Applications

Instantaneous Attachment of an Ultrahigh Density of Nonthiolated DNA to Gold Nanoparticles and Its Applications

Spherical Nucleic Acid Nanoparticle Conjugates Enhance G‐Quadruplex Formation and Increase Serum Protein Interactions

Flow Cytometry-Assisted Detection of Adenosine in Serum with an Immobilized Aptamer Sensor

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