Endogenous Enzyme‐Operated Spherical Nucleic Acids for Cell‐Selective Protein Capture and Localization Regulation

Abstract

Precise regulation of protein activity and localization in cancer cells is crucial to dissect the function of the protein‐involved cellular network in tumorigenesis, but there is a lack of suitable methodology. Here we report the design of enzyme‐operated spherical nucleic acids (E‐SNAs) for manipulation of the nucleocytoplasmic translocation of proteins with cancer‐cell selectivity. The E‐SNAs are constructed by programmable engineering of aptamer‐based modules bearing enzyme‐responsive units in predesigned sites and further combination with SNA nanotechnology. We demonstrate that E‐SNAs are able to regulate cytoplasmic‐to‐nuclear shuttling of RelA protein efficiently and specifically in tumor cells, while they remain inactive in normal cells due to insufficient enzyme expression. We further confirmed the generality of this strategy by investigating the enzyme‐modulated inhibition/activation of thrombin activity by varying the aptamer‐based design.

Efficient Three-Dimensional DNA Nanomachine Guided by a Robust Tetrahedral DNA Nanoarray Structure for the Rapid and Ultrasensitive Electrochemical Detection of Matrix Metalloproteinase 2

“…At present, most of the reported DNA walkers, such as one-dimensional (1D) , and two-dimensional (2D) DNA walkers, , are faced with difficulties of the limited number and length of arms resulting in the derailment of the DNA walker, further restricting the whole reaction rate and sensing efficiency. On account of these drawbacks, three-dimensional (3D) DNA nanomachines immobilized on the surface of AuNPs and magnetic beads (MBs) were proposed. , Benefiting from their high DNA-loading capability, they definitely improved the walking speed and signal amplification efficiency to some extent, but some remaining problems still cannot be ignored. The majority of the traditional 3D DNA nanomachines not only moved on the disordered DNA tracks composed of two-dimensional (2D) or one-dimensional (1D) single-stranded (ss)­DNA probes, , but also walked in a ″step-by-step″ fashion with a limited number and length of arms, , which readily led to a deviation from the designed tracks so as to greatly limit the amplification efficiency and slow down the walking rate of the 3D DNA nanomachines.…”

Magnetic Bead Spherical Nucleic Acid Microstructure for Reliable DNA Preservation and Repeated DNA Reading

“…26−28 The unique three-dimensional (3D) architecture of SNAs protects the oligonucleotides from nuclease-mediated degradation, increases oligonucleotide bioavailability, and facilitates special molecular recognition with a binding affinity a hundred times higher for complementary sequences compared with their linear counterparts. 29,30 SNAs also offer a practical and suitable vector for a variety of nucleic acid amplifications, including the polymerase chain reaction (PCR). 31,32 These advantages make SNAs an excellent biomedicine platform that has been widely used for gene/immune therapy, biosensing, and bioimaging in the past.…”

“…To tackle the present problems with DNA storage, it is essential to develop a platform that can support the repeated reading of DNA information while also protecting it. Spherical nucleic acids (SNAs) are composed of a particle core and a shell of densely arranged, oriented oligonucleotides. − Oligonucleotides can be attached to the particle core in a covalent or noncovalent manner through a linker moiety. − The unique three-dimensional (3D) architecture of SNAs protects the oligonucleotides from nuclease-mediated degradation, increases oligonucleotide bioavailability, and facilitates special molecular recognition with a binding affinity a hundred times higher for complementary sequences compared with their linear counterparts. , SNAs also offer a practical and suitable vector for a variety of nucleic acid amplifications, including the polymerase chain reaction (PCR). , These advantages make SNAs an excellent biomedicine platform that has been widely used for gene/immune therapy, biosensing, and bioimaging in the past. − To the best of our knowledge, the applications of SNAs as reliable DNA storage platforms are seldom.…”