巯基-二硫键交换作为聚合物纳米颗粒进入内涵体的途径。
Thiol-Disulfide Exchange as a Route for Endosomal Escape of Polymeric Nanoparticles.
机构信息
Department of Chemistry, University of Massachusetts Amherst, Amherst, MA 01003, USA.
Department of Biomedical Engineering, Molecular and Cellular Biology Program, and Centre for Bioactive Delivery-Institute for Applied Life Sciences, University of Massachusetts Amherst, Amherst, MA 01003, USA.
出版信息
Angew Chem Int Ed Engl. 2022 Sep 12;61(37):e202209227. doi: 10.1002/anie.202209227. Epub 2022 Aug 8.
Abstract
Endosomal entrapment has remained the major bottleneck for cytosolic delivery of nanoparticle-based delivery systems. Uncovering fundamentally new pathways for endosomal escape is therefore highly sought. Herein, we report that disulfide bonds can enhance endosomal escape through contacts with cellular exofacial thiols, in addition to facilitating cellular uptake. Our results are supported through comparative analysis of polymeric nanogels with variable accessibility to disulfide bonds by placing these functionalities at the core or the shell of the nanogels. The findings here inform future chemical design of delivery vehicles.
摘要
内体捕获仍然是基于纳米粒子的递药系统实现胞质递送的主要瓶颈。因此，人们强烈追求发现用于内体逃逸的全新途径。在此，我们报告二硫键除了促进细胞摄取外，还可以通过与细胞外表面硫醇接触来增强内体逃逸。我们的结果通过将这些功能置于纳米凝胶的核或壳中，以改变纳米凝胶中二硫键的可及性，对具有不同二硫键可及性的聚合物纳米凝胶进行比较分析得到支持。这些发现为递药载体的未来化学设计提供了信息。
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