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DNA origami nanostructures (DOs) are promising tools for applications including drug delivery, biosensing, detecting biomolecules, and probing chromatin substructures. Targeting these nanodevices to mammalian cell nuclei could provide impactful approaches for probing, visualizing, and controlling biomolecular processes within live cells. We present an approach to deliver DOs into live-cell nuclei. We show that these DOs do not undergo detectable structural degradation in cell culture media or cell extracts for 24 hours. To deliver DOs into the nuclei of human U2OS cells, we conjugated 30-nanometer DO nanorods with an antibody raised against a nuclear factor, specifically the largest subunit of RNA polymerase II (Pol II). We find that DOs remain structurally intact in cells for 24 hours, including inside the nucleus. We demonstrate that electroporated anti–Pol II antibody–conjugated DOs are piggybacked into nuclei and exhibit subdiffusive motion inside the nucleus. Our results establish interfacing DOs with a nuclear factor as an effective method to deliver nanodevices into live-cell nuclei. 

A disintegrin and metalloproteinase 17 (ADAM17) has become a novel biomarker and potential therapeutic target for the early detection and treatment of human cancers. In this work, by covalently attaching fluorescently labeled ADAM17 substrate peptide (Pep-FAM) molecules to carboxylated graphene oxide (cGO) and monitoring the cleavage of the peptide substrate by ADAM17, we developed a cGO-Pep-FAM fluorescence sensor for the rapid, sensitive and accurate detection of ADAM17. The sensor was highly sensitive with a detection limit of 17.5 picomolar. Furthermore, the sensor was selective: structure similar proteases such as ADAM9 and MMP-9 would not interfere with ADAM17 detection. In addition, simulated serum samples were successfully analyzed. Our developed cGO-Pep-FAM sensing strategy should find useful applications in disease diagnosis and drug screening. 

To overcome the effect of other components of complicated biological samples on nanopore stochastic sensing, displacement chemical reaction was utilized to selectively extract the target nucleic acid from whole blood. Given its simplicity and high sensitivity for detecting nucleic acids, our developed displacement chemistry-based nanopore sensing strategy offers the potential for fieldable/point-of-care diagnostic applications.