Amplified Analysis of DNA by the Autonomous Assembly of Polymers Consisting of DNAzyme Wires

Wang, Fuan; Elbaz, Johann; Orbach, Ron; Magen, Nimrod; Willner, Itamar

doi:10.1021/ja2076789

Cited by 325 publications

(213 citation statements)

References 36 publications

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“…Graphene-based composites may combine the outstanding properties of graphene with the special functions of the other components. There have been many attempts to synthesize hybrid structures of graphene and Au nanoparticles (Muszynski et al, 2008;Coros et al, 2013;Chen et al, 2011a) which have been widely utilized in the fields of electrochemical biosensor (Hu et al, 2012;Du et al, 2010;Gautam and Jayatissa, 2012;Wang et al, 2011b). Au nanorods (Au NR) could exhibit the advantages of sensor devices due to their tunable and stronger Vis/NIR absorption, higher surface-enhanced Raman scattering cross-sections, and the possibility of unidirectional plasmon propagation .…”

Section: Introductionmentioning

confidence: 99%

An ultrasensitive electrochemical DNA biosensor based on graphene/Au nanorod/polythionine for human papillomavirus DNA detection

Huang

Bai

Dong

et al. 2015

Biosensors and Bioelectronics

187

101

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Section: Introductionmentioning

confidence: 99%

An ultrasensitive electrochemical DNA biosensor based on graphene/Au nanorod/polythionine for human papillomavirus DNA detection

Huang

Bai

Dong

et al. 2015

Biosensors and Bioelectronics

187

101

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“…1A). The programmable, periodic, and biodegradable nature of these nanostructures provides unprecedented opportunities for biomedical applications (30)(31)(32). The conditional formation of aptNTrs upon initiation from engineered aptamertrigger probes ensures that each resultant nanotrain is tethered with an aptamer moiety on one end of the nanoconstruct.…”

mentioning

confidence: 99%

Self-assembled, aptamer-tethered DNA nanotrains for targeted transport of molecular drugs in cancer theranostics

Zhu

Zheng

Song

et al. 2013

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

506

395

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Nanotechnology has allowed the construction of various nanostructures for applications, including biomedicine. However, a simple target-specific, economical, and biocompatible drug delivery platform with high maximum tolerated doses is still in demand. Here, we report aptamer-tethered DNA nanotrains (aptNTrs) as carriers for targeted drug transport in cancer therapy. Long aptNTrs were selfassembled from only two short DNA upon initiation by modified aptamers, which worked like locomotives guiding nanotrains toward target cancer cells. Meanwhile, tandem "boxcars" served as carriers with high payload capacity of drugs that were transported to target cells and induced selective cytotoxicity. aptNTrs enhanced maximum tolerated dose in nontarget cells. Potent antitumor efficacy and reduced side effects of drugs delivered by biocompatible aptNTrs were demonstrated in a mouse xenograft tumor model. Moreover, fluorophores on nanotrains and drug fluorescence dequenching upon release allowed intracellular signaling of nanotrains and drugs. These results make aptNTrs a promising targeted drug transport platform for cancer theranostics. A lthough chemotherapeutic drugs are widely used in cancer therapy, they lack specificity and can induce cytotoxicity in both cancerous and healthy cells, causing side effects (1), limited maximum tolerated dose (MTD), and reduced therapeutic efficacy (2, 3). A theranostic (4) platform with targeted and efficient drug transport would solve these problems, and, by its programmability, DNA nanotechnology has been used for the rational assembly of one-, two-, and three-dimensional nanostructures (5-8), which have been further studied for biomedical applications, including the passive targeted transport of theranostic agents (9-17). In addition, aptamers, as specific recognition elements, have been studied for active targeted transport of conventional chemotherapeutic drugs (11,12,(18)(19)(20)(21). Nucleic acid aptamers are single-stranded oligonucleotides with unique intramolecular conformations and specific recognition abilities to cognate targets, including mammalian cancer cells (22-26). Recent biotechnological advancements have led to a variety of targeted drug transport (TDT) strategies based on aptamer-drug conjugates or aptamer-nanomaterial assemblies (11,12,(18)(19)(20)(21)27). However, these strategies have unique limitations that could hamper the transition to clinical application, including (i) complicated design, laborious and uneconomical bulky preparation of myriad ssDNA as building blocks to construct sophisticated nucleic acid-based nanomaterials, or laborious and inefficient preparation of aptamer-drug conjugates (9,11,14,15,17,18); (ii) limited drug payload capacity and the attendant high cost, hampering production scale-up (9,11,14,15,17,18,20,27); (iii) poor biodegradability, causing chronic accumulation of nanomaterials in vivo (28, 29); and (iv) limited universality by the requirement of specific aptamer for drug loading (20).However, we have designed and engineered a DNA ...

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“…However, electrochemical detection schemes have typically been restricted to measurements of highly purified samples because of the increased congestion and decreased accessibility of surface (vs. solution) platforms. Electrochemistry has been used to detect nucleic acids with high sensitivity and without the need for PCR amplification in bacterial lysate and serum (18)(19)(20)(21)(22), but protein detection remains a challenge (23)(24)(25)(26). In fact, although protein detection from simple serum has been accomplished (27,28), to date no reported electrochemical systems have effectively detected active protein, of any kind, from crude cell lysate.…”

mentioning

confidence: 99%

Label-free electrochemical detection of human methyltransferase from tumors

Furst

Muren

Hill

et al. 2014

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

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The role of abnormal DNA methyltransferase activity in the development and progression of cancer is an essential and rapidly growing area of research, both for improved diagnosis and treatment. However, current technologies for the assessment of methyltransferase activity, particularly from crude tumor samples, limit this work because they rely on radioactivity or fluorescence and require bulky instrumentation. Here, we report an electrochemical platform that overcomes these limitations for the label-free detection of human DNA(cytosine-5)-methyltransferase1 (DNMT1) methyltransferase activity, enabling measurements from crude cultured colorectal cancer cell lysates (HCT116) and biopsied tumor tissues. Our multiplexed detection system involving patterning and detection from a secondary electrode array combines low-density DNA monolayer patterning and electrocatalytically amplified DNA charge transport chemistry to measure selectively and sensitively DNMT1 activity within these complex and congested cellular samples. Based on differences in DNMT1 activity measured with this assay, we distinguish colorectal tumor tissue from healthy adjacent tissue, illustrating the effectiveness of this two-electrode platform for clinical applications.DNA electrochemistry | methylation detection | electrocatalysis

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Amplified Analysis of DNA by the Autonomous Assembly of Polymers Consisting of DNAzyme Wires

Cited by 325 publications

References 36 publications

An ultrasensitive electrochemical DNA biosensor based on graphene/Au nanorod/polythionine for human papillomavirus DNA detection

An ultrasensitive electrochemical DNA biosensor based on graphene/Au nanorod/polythionine for human papillomavirus DNA detection

Self-assembled, aptamer-tethered DNA nanotrains for targeted transport of molecular drugs in cancer theranostics

Label-free electrochemical detection of human methyltransferase from tumors

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