Bioorthogonal Disassembly of Tetrazine Bearing Supramolecular Assemblies Inside Living Cells.
Bioorthogonal Disassembly of Tetrazine Bearing Supramolecular Assemblies Inside Living Cells.
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DOI：
10.1002/smll.202104772
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发表时间：
2021-11
期刊：
影响因子：
13.3
通讯作者：
Jialei Song;Chengling Wu;Yan Zhao;Min Yang;Qingxin Yao;Yuan Gao
中科院分区：
文献类型：
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作者：
Jialei Song;Chengling Wu;Yan Zhao;Min Yang;Qingxin Yao;Yuan Gao
超分子组装体是用于药物输送系统（DDS）的一类新兴纳米材料，但它们在生物环境中的意外滞留在很大程度上仍未得到解决。为了实现超分子组装体的快速清除，本文研究了活细胞内超分子组装体的分解和清除的生物正交反应。设计了一系列四嗪封端的组装前体，它们可以在酶促去磷酸化后自组装成纳米纤维和水凝胶。这种酶指导的超分子组装过程可以在细胞内进行。组件的时间依赖性积累会引发氧化应激并诱导细胞毒性。含四嗪的组件与反式环辛烯衍生物发生反应，导致 π-π 堆积破坏并引起分解。这样，细胞内的自组装体就会分解并失去效力。这种生物正交拆卸策略在开发 DDS 纳米材料时利用了生物安全性。
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.