Enzymatic Control of Plasmonic Coupling and Surface Enhanced Raman Scattering Transduction for Sensitive Detection of DNA Demethylation

Abstract

We have developed a novel concept for enzymatic control of plasmonic coupling as a surface enhanced Raman scattering (SERS) nanosensor for DNA demethylation. This nanosensor is constructed by decorating gold nanoparticles (AuNPs) with Raman reporters and hemimethylated DNA probes. Demethylation of DNA probes initiates a degradation reaction of the probes by methylation-sensitive endonuclease Bsh 1236I and single-strand selective exonuclease I. This destabilizes AuNPs and mediates the aggregation of AuNPs, generating a strong plasmonic coupling SERS signal in response to DNA demethylation. This nanosensor has the advantages in its high signal-to-noise ratio, superb specificity, and rapid, convenient, and reproducible detection with homogeneous, single-step operation. Thus, it provides a useful platform for detecting DNA demethylation and related molecular diagnostics and drug screening. This work is the first time that enzymatic degradation of DNA substrate probes has been utilized to induce aggregation of AuNPs such that reproducible, sensitive SERS signals can be achieved from biological recognition events. This enzymatic control mechanism for plasmonic coupling may create a new paradigm for the development of SERS nanosensors.

Applications of gold nanoparticles in medicine and therapy

“…70,71 Wang et al 72 raised a concept to use enzyme controlled plasmonic coupling as SERS nanosensors for DNA demethylation. 72 The nanosensors were constructed by decorating AuNPs with Raman reporters and hemimethylated DNA probes.…”

“…70,71 Wang et al 72 raised a concept to use enzyme controlled plasmonic coupling as SERS nanosensors for DNA demethylation. 72 The nanosensors were constructed by decorating AuNPs with Raman reporters and hemimethylated DNA probes. The enzymatic degradation of DNA substrate probes was utilized to induce aggregation of AuNPs, so the reproducible and sensitive SERS signals were achieved from biological recognition events.…”

Advanced AuNMs as nanomedicine’s central goals capable of active targeting in both imaging and therapy in biomolecules

“…Wang et al [66] raised a concept to use enzyme controlled plasmonic coupling as SERS nanosensors for DNA demethylation. The nanosensors were constructed by decorating AuNPs with Raman reporters and hemimethylated DNA probes.…”

Revealing and Resolving the Restrained Enzymatic Cleavage of DNA Self-Assembled Monolayers on Gold: Electrochemical Quantitation and ESI-MS Confirmation

“…[4][5][6] Benefited from this unique property, Exo I has been extensively employed in nucleic acid biochemistry and genetic engineering, such as DNA mutation repair/avoidance, 7 PCR primer digestion, 8 and DNA demethylation detection. 9 Recently, Exo I has been creatively introduced to and popularly utilized in the fabrication of biosensors as an effective tool for improving their sensitivities and selectivities. [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] For example, Jiang and co-workers developed a universal Exo I-assisted terminal protection protocol for detecting various targets of interest.…”