Bioorthogonal Disassembly of Tetrazine Bearing Supramolecular Assemblies Inside Living Cells
Jialei Song
CAS Center for Excellence in Nanoscience, CAS Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, 100190 China
Sino-Danish Center for Education and Research, University of Chinese Academy of Sciences, Beijing, 100049 China
Search for more papers by this authorChengling Wu
CAS Center for Excellence in Nanoscience, CAS Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, 100190 China
Search for more papers by this authorYan Zhao
CAS Center for Excellence in Nanoscience, CAS Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, 100190 China
Search for more papers by this authorMin Yang
CAS Center for Excellence in Nanoscience, CAS Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, 100190 China
Search for more papers by this authorCorresponding Author
Qingxin Yao
CAS Center for Excellence in Nanoscience, CAS Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, 100190 China
E-mail: [email protected], [email protected]
Search for more papers by this authorCorresponding Author
Yuan Gao
CAS Center for Excellence in Nanoscience, CAS Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, 100190 China
Sino-Danish Center for Education and Research, University of Chinese Academy of Sciences, Beijing, 100049 China
E-mail: [email protected], [email protected]
Search for more papers by this authorJialei Song
CAS Center for Excellence in Nanoscience, CAS Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, 100190 China
Sino-Danish Center for Education and Research, University of Chinese Academy of Sciences, Beijing, 100049 China
Search for more papers by this authorChengling Wu
CAS Center for Excellence in Nanoscience, CAS Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, 100190 China
Search for more papers by this authorYan Zhao
CAS Center for Excellence in Nanoscience, CAS Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, 100190 China
Search for more papers by this authorMin Yang
CAS Center for Excellence in Nanoscience, CAS Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, 100190 China
Search for more papers by this authorCorresponding Author
Qingxin Yao
CAS Center for Excellence in Nanoscience, CAS Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, 100190 China
E-mail: [email protected], [email protected]
Search for more papers by this authorCorresponding Author
Yuan Gao
CAS Center for Excellence in Nanoscience, CAS Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, 100190 China
Sino-Danish Center for Education and Research, University of Chinese Academy of Sciences, Beijing, 100049 China
E-mail: [email protected], [email protected]
Search for more papers by this authorAbstract
Supramolecular assemblies are an emerging class of nanomaterials for drug delivery systems (DDS), while their unintended retention in the biological milieu remains largely unsolved. To realize the prompt clearance of supramolecular assemblies, the bioorthogonal reaction to disassemble and clear the supramolecular assemblies within living cells is investigated here. A series of tetrazine-capped assembly precursors which can self-assemble into nanofibers and hydrogels upon enzymatic dephosphorylation are designed. Such an enzyme-instructed supramolecular assembly process can perform intracellularly. The time-dependent accumulation of assemblies elicits oxidative stress and induces cellular toxicity. Tetrazine-bearing assemblies react with trans-cyclooctene derivatives, which lead to the disruption of π–π stacking and induce disassembly. In this way, the intracellular self-assemblies disassemble and are deprived of potency. This bioorthogonal disassembly strategy leverages the biosafety aspect in developing nanomaterials for DDSs.
Conflict of Interest
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
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smll202104772-sup-0001-SuppMat.pdf3 MB | Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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