Selective Enhancement of Nucleases by Polyvalent DNA-Functionalized Gold Nanoparticles

Prigodich, Andrew E.; Alhasan, Ali H.; Mirkin, Chad A.

doi:10.1021/ja110833r

Cited by 119 publications

(144 citation statements)

References 39 publications

(23 reference statements)

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“…S3A). These findings suggest that high grafting density of DNA on a nanoparticle surface increases its resistance to serum degradation, consistent with what was observed for GNP-DNA degradation by DNase I (14,15) and GNP-RNA serum degradation (19)(20)(21)(22).…”

Section: Resultssupporting

confidence: 86%

Controlling DNA–nanoparticle serum interactions

Zagorovsky

Chou

Chan

2016

Proc. Natl. Acad. Sci. U.S.A.

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Understanding the interaction of molecularly assembled nanoparticles with physiological fluids is critical to their use for in vivo delivery of drugs and contrast agents. Here, we systematically investigated the factors and mechanisms that govern the degradation of DNA on the nanoparticle surface in serum. We discovered that a higher DNA density, shorter oligonucleotides, and thicker PEG layer increased protection of DNA against serum degradation. Oligonucleotides on the surface of nanoparticles were highly resistant to DNase I endonucleases, and degradation was carried out exclusively by protein-mediated exonuclease cleavage and full-strand desorption. These results enabled the programming of the degradation rates of the DNA-assembled nanoparticle system from 0.1 to 0.7 h −1 and the engineering of superstructures that can release two different preloaded dye molecules with distinct kinetics and half-lives ranging from 3.3 to 9.8 h. This study provides a general framework for investigating the serum stability of DNA-containing nanostructures. The results advance our understanding of engineering principles for designing nanoparticle assemblies with controlled in vivo behavior and present a strategy for storage and multistage release of drugs and contrast agents that can facilitate the diagnosis and treatment of cancer and other diseases.nanoparticle assembly | DNA nanostructures | serum stability | serum resistance | controlled cargo release

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Section: Resultssupporting

confidence: 86%

Controlling DNA–nanoparticle serum interactions

Zagorovsky

Chou

Chan

2016

Proc. Natl. Acad. Sci. U.S.A.

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“…In other words, enhanced activity can be attributed to the fact that with each collision between NP-immobilized enzymes and free-floating substrate, the weak association between the substrate and the NP interface results in multiple binding occurrences on one NP before the substrate moves elsewhere [31]. This proposed substrate-NP association or attraction would subsequently lead to a higher concentration of substrate near the periphery of the NP as opposed to the bulk environment which would further enhance the activity of enzymes immobilized on NPs than floating free in solution [32]. This motion is described in the literature as a process in which first reversible adsorption of the enzyme onto the NP surface takes place, followed by complete digestion of the substrate onto the NP, and finally desorption of the substrate for similar interactions with other NPs [21 ].…”

Section: Introductionmentioning

confidence: 99%

Increasing the activity of immobilized enzymes with nanoparticle conjugation

Ding¹,

Cargill²,

Medintz³

et al. 2015

Current Opinion in Biotechnology

244

153

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The efficiency and selectivity of enzymatic catalysis is useful to a plethora of industrial and manufacturing processes. Many of these processes require the immobilization of enzymes onto surfaces, which has traditionally reduced enzyme activity. However, recent research has shown that the integration of nanoparticles into enzyme carrier schemes has maintained or even enhanced immobilized enzyme performance. The nanoparticle size and surface chemistry as well as the orientation and density of immobilized enzymes all contribute to the enhanced performance of enzyme-nanoparticle conjugates. These improvements are noted in specific nanoparticles including those comprising carbon (e.g., graphene and carbon nanotubes), metal/metal oxides and polymeric nanomaterials, as well as semiconductor nanocrystals or quantum dots.

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“…These constructs have been shown to enter over 60 cell lines and primary cells tested to date, and they are believed to do so by engaging scavenger receptors that facilitate caveolin-mediated endocytosis (15). They are also stable to nuclease degradation (18), lack cytotoxicity (19), and are effective for single-gene or multigene detection from a single nanoconstruct (20). Nanoflares, when coupled with flow cytometry, can be used to isolate cells with a target gene in the context of a greater cell population.…”

Section: Introductionmentioning

confidence: 99%

Application of a nanoflare probe specific to a latency associated transcript for isolation of KHV latently infected cells

et al. 2015

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One of the unique features of herpesvirus infection is latent infection following an initial exposure, which is characterized by viral genome persistence in a small fraction of cells within the latently infected tissue. Investigation of the mechanisms of herpesvirus latency has been very challenging in tissues with only a small fraction of cells that are latently infected. Cyprinid herpesvirus 3, also known as koi herpesvirus (KHV), is an important and deadly pathogen of koi and common carp, Cyprinus carpio. Acute infection can cause up to 100% mortality in exposed fish, and fish that survive the infection become latently infected. KHV becomes latent in a small percentage of B lymphocytes and can reactivate under stressful conditions. During latency, KHV ORF6 transcript is expressed in the latently infected B lymphocytes. In order to study KHV latent infection in cells that are only latently infected, a nanoflare probe specific to ORF6 RNA was used to separate KHV latently infected cells from total peripheral white blood cells (WBC). Using the ORF6 nanoflare probe, less than 1% of peripheral WBC was isolated from KHV latently infected koi. When this enriched population of WBC was examined by real-time PCR specific for KHV, it was estimated that about 1 to 2 copies of viral genome persists in the sorted cells. In addition, KHV ORF6 transcript was shown to be the major transcript expressed during latency by RNA-seq analysis. This study demonstrated that an RNA nanoflare probe could be used to enrich latently infected cells, which can subsequently be used to investigate the molecular mechanisms of KHV latency.

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Selective Enhancement of Nucleases by Polyvalent DNA-Functionalized Gold Nanoparticles

Cited by 119 publications

References 39 publications

Controlling DNA–nanoparticle serum interactions

Controlling DNA–nanoparticle serum interactions

Increasing the activity of immobilized enzymes with nanoparticle conjugation

Application of a nanoflare probe specific to a latency associated transcript for isolation of KHV latently infected cells

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