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Extracellular Microreactor for the Depletion of Phenylalanine Toward Phenylketonuria Treatment

机译：细胞外微反应器用于苯丙氨酸耗竭苯丙酮尿症的治疗

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摘要

Phenylketonuria (PKU) is a genetic enzyme defect affecting 1:10 000-20 000 newborn children every year. The amino acid phenylalanine (Phe) is not depleted but accumulates in tissues of several organs, which leads to severe medical conditions. A promising concept to restore the metabolism of the affected patients will be to orally administer the defective enzyme which will remove Phe in the intestine. Herein, capsosomes, a multicompartment carrier consisting of thousands of liposomes embedded within a polymeric carrier, are employed as encapsulation platform for this purpose. It is shown that the enzyme phenylalanine ammonia lyase can be entrapped within the liposomal compartments with preserved activity, demonstrated by the conversion of Phe into trans-cinnamic acid (t-ca). With the aim to mimic the dynamic environment in the intestine, the Phe conversion is performed in a microfluidic set up in the presence of human intestinal epithelial cells with applied intestinal flow and peristaltic motions. It is also shown that the microreactors are neither internalized by the cells nor exhibit inherent cytotoxicity while concurrently converting Phe into t-ca. Taken together, the first active extracellular multicompartment microreactor is reported using the relevant enzymes and settings toward the treatment of the medical condition PKU.
机译：苯丙酮尿症（PKU）是一种遗传酶缺陷，每年影响1:10 000-20 000新生儿童。氨基酸苯丙氨酸（Phe）并未耗尽，但会积聚在多个器官的组织中，从而导致严重的医疗状况。恢复患病患者新陈代谢的一个有前途的概念将是口服施用有缺陷的酶，该酶将去除肠道中的苯丙氨酸。在本文中，衣囊体是由嵌入聚合物载体中的数千种脂质体组成的多室载体，用作该目的的包囊平台。结果表明，苯丙氨酸氨裂合酶可以被保留在脂质体区室中，并且具有保留的活性，这可以通过将Phe转化为反式肉桂酸（t-ca）来证明。为了模拟肠道中的动态环境，Phe转化是在存在人类肠道上皮细胞并施加肠道流动和蠕动的情况下，在微流体装置中进行的。还显示微反应器既不被细胞内化也不显示固有的细胞毒性，同时将Phe转化为t-ca。综上所述，第一个活性的细胞外多室微反应器被报道使用相关的酶和用于治疗PKU的设置。

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