Department of Urology, The First Affiliated Hospital, Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, People's Republic of China.
Nanotechnology. 2013 Sep 20;24(37):375102. doi: 10.1088/0957-4484/24/37/375102. Epub 2013 Aug 23.
Directed enzyme/prodrug therapy (DEPT) has promising application for cancer therapy. However, most current DEPT strategies face shortcomings such as the loss of enzyme activity during preparation, low delivery and transduction efficiency in vivo and difficultly of monitoring. In this study, a novel magnetic directed enzyme/prodrug therapy (MDEPT) was set up by conjugating β-glucosidase (β-Glu) to aminated, starch-coated, iron oxide magnetic iron oxide nanoparticles (MNPs), abbreviated as β-Glu-MNP, using glutaraldehyde as the crosslinker. This β-Glu-MNP was then characterized in detail by size distribution, zeta potential, FTIR spectra, TEM, SQUID and magnetophoretic mobility analysis. Compared to free enzyme, the conjugated β-Glu on MNPs retained 85.54% ± 6.9% relative activity and showed much better temperature stability. The animal study results showed that β-Glu-MNP displays preferable pharmacokinetics characteristics in relation to MNPs. With an adscititious magnetic field on the surface of a tumor, a significant quantity of β-Glu-MNP was selectively delivered into a subcutaneous tumor of a glioma-bearing mouse. Remarkably, the enzyme activity of the delivered β-Glu in tumor lesions showed as high as 20.123±5.022 mU g(-1) tissue with 2.14 of tumor/non-tumor β-Glu activity.
导向酶/前药疗法（DEPT）在癌症治疗中有很好的应用前景。然而，大多数当前的 DEPT 策略都面临着一些缺点，例如在制备过程中酶活性的丧失、体内递送和转导效率低以及难以监测。在这项研究中，通过用戊二醛作为交联剂将β-葡糖苷酶（β-Glu）偶联到氨基化、淀粉涂层的氧化铁磁性纳米颗粒（MNPs）上，建立了一种新型的磁性导向酶/前药疗法（MDEPT），简称β-Glu-MNP。然后通过粒径分布、zeta 电位、FTIR 光谱、TEM、SQUID 和磁泳动分析对β-Glu-MNP 进行了详细的表征。与游离酶相比，结合在 MNPs 上的共轭β-Glu保留了 85.54%±6.9%的相对活性，并且表现出更好的温度稳定性。动物研究结果表明，与 MNPs 相比，β-Glu-MNP 具有更好的药代动力学特性。在肿瘤表面施加外加磁场后，大量的β-Glu-MNP 被选择性地递送到荷胶质瘤小鼠的皮下肿瘤中。值得注意的是，输送到肿瘤病变中的β-Glu 的酶活性高达 20.123±5.022 mU g(-1) 组织，肿瘤/非肿瘤β-Glu 活性为 2.14。
