Department of Chemistry, University of Massachusetts, Amherst, MA, 01003, USA.
Department of Food Science, University of Massachusetts, Amherst, MA, 01003, USA.
Angew Chem Int Ed Engl. 2020 Aug 24;59(35):15135-15140. doi: 10.1002/anie.202004017. Epub 2020 Jun 15.
Polymer-drug conjugates are promising as strategies for drug delivery, because of their high drug loading capacity and low premature release profile. However, the preparation of these conjugates is often tedious. In this paper, we report an efficient method for polymer-drug conjugates using an ultrafast and reversible click reaction in a post-polymerization functionalization strategy. The reaction is based on the rapid condensation of boronic acid functionalities with salicylhydroxamates. The polymer, bearing the latter functionality, has been designed such that the reaction with boronic acid bearing drugs induces an in situ self-assembly of the conjugates to form well-defined nanostructures. We show that this method is not only applicable for molecules with an intrinsic boronic acid group, but also for the other molecules that can be linked to aryl boronic acids through a self-immolative linker. The linker has been designed to cause traceless release of the attached drug molecules, the efficiency of which has been demonstrated through intracellular delivery.
聚合物-药物偶联物作为药物递送的策略很有前景，因为它们具有高载药能力和低早期释放特性。然而，这些偶联物的制备通常很繁琐。在本文中，我们报告了一种使用超快和可逆点击反应的聚合物-药物偶联物的有效方法，该方法基于硼酸官能团与水杨羟肟酸的快速缩合。具有后一种官能团的聚合物被设计成与带有硼酸的药物反应，诱导偶联物的原位自组装形成明确定义的纳米结构。我们表明，该方法不仅适用于具有内在硼酸基团的分子，也适用于可以通过自牺牲连接子与芳基硼酸连接的其他分子。该连接子被设计为无痕迹释放附着的药物分子，通过细胞内递送来证明其效率。
