Department of Micro- and Nanotechnology, Centre for Nanomedicine and Theranostics, DTU Nanotech, Technical University of Denmark , Building 423, 2800, Lyngby, Denmark.
ACS Appl Mater Interfaces. 2017 May 17;9(19):15907-15921. doi: 10.1021/acsami.6b16275. Epub 2017 Feb 13.
Cell organelles are subcellular structures entrapping a set of enzymes to achieve a specific functionality. The incorporation of artificial organelles into cells is a novel medical paradigm which might contribute to the treatment of various cell disorders by replacing malfunctioning organelles. In particular, artificial organelles are expected to be a powerful solution in the context of enzyme replacement therapy since enzymatic malfunction is the primary cause of organelle dysfunction. Although several attempts have been made to encapsulate enzymes within a carrier vehicle, only few intracellularly active artificial organelles have been reported to date and they all consist of single-compartment carriers. However, it is noted that biological organelles consist of multicompartment architectures where enzymatic reactions are executed within distinct subcompartments. Compartmentalization allows for multiple processes to take place in close vicinity and in a parallel manner without the risk of interference or degradation. Here, we report on a subcompartmentalized and intracellularly active carrier, a crucial step for advancing artificial organelles. In particular, we develop and characterize a novel capsosome system, which consists of multiple liposomes and fluorescent gold nanoclusters embedded within a polymer carrier capsule. We subsequently demonstrate that encapsulated enzymes preserve their activity intracellularly, allowing for controlled enzymatic cascade reaction within a host cell.
细胞器官是细胞内的亚细胞结构，其中包含一组酶以实现特定的功能。将人工细胞器纳入细胞是一种新的医学范例，通过替换功能失调的细胞器，可能有助于治疗各种细胞疾病。特别是，在酶替代疗法的背景下，人工细胞器有望成为一种强大的解决方案，因为酶功能障碍是细胞器功能障碍的主要原因。尽管已经有几种尝试将酶封装在载体中，但迄今为止仅报道了少数具有细胞内活性的人工细胞器，并且它们都由单室载体组成。然而，值得注意的是，生物细胞器由多室结构组成，其中酶反应在不同的亚室中进行。区室化允许多个过程在近距离和并行的方式下发生，而不会有干扰或降解的风险。在这里，我们报告了一种亚区室化和细胞内活性的载体，这是推进人工细胞器的关键步骤。具体而言，我们开发并表征了一种新型的capsosome 系统，它由多个嵌入聚合物载体胶囊内的脂质体和荧光金纳米簇组成。随后，我们证明了封装的酶在细胞内保持其活性，允许在宿主细胞内进行受控的酶级联反应。
