Volume 18, Issue 2 2104772
Research Article

Bioorthogonal Disassembly of Tetrazine Bearing Supramolecular Assemblies Inside Living Cells

Jialei Song

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

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Chengling Wu

Chengling 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

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Yan Zhao

Yan 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

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Min Yang

Min 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

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Qingxin Yao

Corresponding 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]

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Yuan Gao

Corresponding 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]

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First published: 29 November 2021
Citations: 3

Abstract

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.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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