Ettlinger Romy, Sönksen Marthe, Graf Monika, Moreno Natalia, Denysenko Dmytro, Volkmer Dirk, Kerl Kornelius, Bunzen Hana
Chair of Solid State and Materials Chemistry, Institute of Physics, University of Augsburg, Universitätsstraße 1, D-86159 Augsburg, Germany.
J Mater Chem B. 2018 Oct 28;6(40):6481-6489. doi: 10.1039/c8tb01899e. Epub 2018 Sep 24.
Arsenic trioxide is a double-edged sword: On the one hand it is known as a poison, on the other hand it is used as an anticancer drug. Though effective in the treatment of leukaemia, arsenic trioxide has not been able to be introduced into the treatment of solid tumour entities yet due to its dose-limiting toxicity. However, different in vitro and in vivo studies revealed arsenic trioxide to be a potent agent against different solid tumour entities, including atypical teratoid rhabdoid tumours (ATRT), a paediatric brain tumour entity with a very poor prognosis. To improve the pharmacokinetics and therapeutic efficacy of arsenic trioxide and to reduce its toxic side effects, we propose to use a metal-organic framework (MOF) as a drug carrier material. Herein we report on using a MOF called MFU-4l (Metal-Organic Framework Ulm University), consisting of Zn(ii) ions and bis(1H-1,2,3-triazolo[4,5-b],[4',5'-i])dibenzo[1,4]dioxin ligands, to deliver arsenic trioxide in a form of dihydrogen arsenite anions. The HAsO anions were introduced to the MOF in a nanoparticle formulation via a postsynthetic side ligand exchange. The prepared material was characterised by IR, TGA, XRPD, SEM-EDX, TEM, DLS, ICP-OES and adsorption analysis. The drug release studies at different pH values were carried out as well as cytotoxicity tests with different ATRT cell lines and non-tumorous-control cell lines. The MOF-based material was shown to be a promising candidate for arsenic trioxide drug delivery.
一方面它被认为是一种毒药，另一方面它又被用作抗癌药物。尽管三氧化二砷在治疗白血病方面有效，但由于其剂量限制性毒性，尚未能够被引入实体瘤的治疗中。然而，不同的体外和体内研究表明，三氧化二砷是针对不同实体瘤的有效药物，包括非典型畸胎样横纹肌样瘤（ATRT），这是一种预后非常差的小儿脑肿瘤。为了改善三氧化二砷的药代动力学和治疗效果，并减少其毒副作用，我们建议使用金属有机框架（MOF）作为药物载体材料。在此，我们报告使用一种名为MFU-4l（乌尔姆大学金属有机框架）的MOF，它由锌（II）离子和双（1H-1,2,3-三唑并[4,5-b]，[4',5'-i]）二苯并[1,4]二恶英配体组成，以亚砷酸二氢根阴离子的形式递送三氧化二砷。通过合成后侧配体交换，将HAsO阴离子以纳米颗粒制剂的形式引入到MOF中。通过红外光谱（IR）、热重分析（TGA）、X射线粉末衍射（XRPD）、扫描电子显微镜-能谱分析（SEM-EDX）、透射电子显微镜（TEM）、动态光散射（DLS）、电感耦合等离子体质谱（ICP-OES）和吸附分析对制备的材料进行了表征。进行了不同pH值下的药物释放研究以及对不同ATRT细胞系和非肿瘤对照细胞系的细胞毒性测试。基于MOF的材料被证明是三氧化二砷药物递送的有前途的候选者。
