Endogenous Enzyme-Operated Spherical Nucleic Acids for Cell-Selective Protein Capture and Localization Regulation |
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Authors: | Dr. Qing Liu Yuanyu Huang Prof. Lele Li Prof. Zhengping Li Mengyuan Li |
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Affiliation: | 1. Advanced Research Institute of Multidisciplinary Science, School of Life Science, Beijing Institute of Technology, Beijing, 100081 China;2. CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, 100190 China;3. School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, 100083 China |
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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. |
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Keywords: | Cancer Cell Specificity Enzymes Protein Function Regulation Spherical Nucleic Acids Subcellular Translocation |
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