Department of Materials, Department of Bioengineering, and Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, UK.
Department of Chemistry and iNANO Interdisciplinary Nanoscience Center, Aarhus University, Aarhus, C 8000, Denmark.
Adv Healthc Mater. 2017 Sep;6(17). doi: 10.1002/adhm.201700385. Epub 2017 Jul 12.
Enzyme prodrug therapy (EPT) enables localized conversion of inert prodrugs to active drugs by enzymes. Performance of EPT necessitates that the enzyme remains active throughout the time frame of the envisioned therapeutic application. β-glucuronidase is an enzyme with historically validated performance in EPT, however it retains its activity in biomaterials for an insufficiently long period of time, typically not exceeding 7 d. Herein, the encapsulation of β-glucuronidase in liposomal subcompartments within poly(vinyl alcohol) electrospun fibers is reported, leading to the assembly of biocatalytically active materials with activity of the enzyme sustained over at least seven weeks. It is further shown that liposomes provide the highly beneficial stabilization of the enzyme when incubated in cell culture media. The assembled biocatalytic materials successfully produce antiproliferative drugs (SN-38) using externally administered prodrugs (SN-38-glucuronide) and effectively suppress cell proliferation, with envisioned utility in the design of cardiovascular grafts.
酶前药疗法（EPT）通过酶使无活性的前药转化为活性药物，从而实现局部转化。EPT 的性能要求酶在预期治疗应用的时间范围内保持活性。β-葡糖苷酸酶是一种在 EPT 中具有经过验证的性能的酶，但它在生物材料中的活性持续时间不够长，通常不超过 7 天。在此，报告了将β-葡糖苷酸酶包封在聚（乙烯醇）电纺纤维中的脂质体亚隔室内，从而组装了具有生物催化活性的材料，其中酶的活性至少持续七周。进一步表明，当在细胞培养基中孵育时，脂质体为酶提供了高度有益的稳定性。组装的生物催化材料成功地使用外部给予的前药（SN-38-葡糖苷酸）产生了抗增殖药物（SN-38），并有效地抑制了细胞增殖，有望用于心血管移植物的设计。
