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.
Small. 2022 Jan;18(2):e2104772. doi: 10.1002/smll.202104772. Epub 2021 Nov 29.
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.
超分子组装体是一类新兴的药物传递系统（DDS）纳米材料，而它们在生物环境中意外滞留的问题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，本研究考察了用于在活细胞内进行组装体解组装和清除的生物正交反应。设计了一系列带有叠氮基团的组装前体，这些前体在酶去磷酸化后可以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。组装体的时间依赖性积累会引发氧化应激并诱导细胞毒性。带有叠氮基团的组装体与反式环辛烯衍生物反应，导致 π-π 堆积的破坏并诱导解组装。通过这种方式，细胞内的自组装体解组装并失去效力。这种生物正交的解组装策略利用了纳米材料在 DDS 开发中的生物安全性方面。
