Polymer Research Laboratory, Department of Organic and Biochemistry, Faculty of Chemistry, University of Tabriz, Tabriz, Iran.
Polymer Research Laboratory, Department of Organic and Biochemistry, Faculty of Chemistry, University of Tabriz, Tabriz, Iran; Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Science, Tabriz, Iran.
Int J Pharm. 2022 Sep 25;625:122112. doi: 10.1016/j.ijpharm.2022.122112. Epub 2022 Aug 13.
Commonly the directly administered chemotherapy drugs lack targeting in tumor treatment. Thus, trying to improve cancer treatment efficiency led us to design a new intelligent system for cancer treatment. Considering these, in the current work, at first, the 2-aminoterephthalic acid (NH-BDC) intercalated layered double hydroxides (MgAl-(NH-BDC) LDH) were synthesized simply. Afterward, the in situ growth of the iron-based metal-organic frameworks in the presence of MgAl-(NH-BDC) LDH occurred (MgAl-LDH/Fe-MOF). In the end, the reaction of MgAl-LDH/Fe-MOF with D-mannose (D-Man) achieved the MgAl-LDH/Fe-MOF/D-Man ternary hybrid nanostructure. Scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) analysis confirmed the formation of the monodisperse Fe-MOF with nanosize in the presence of MgAl-LDH. Importantly, methotrexate (MTX) and doxorubicin (DOX) entrapment efficiency reached respectively about 28 wt% and 21% for MgAl-LDH/Fe-MOF/D-Man. The in vitro drug release experiments revealed a higher drug release at pH 5.0 in comparison with pH 7.4 which revealed its promising potential for anticancer drug delivery applications. Bioassay results revealed that the co-drug-loaded MgAl-LDH/Fe-MOF/D-Man has higher cytotoxicity on MDA-MB 231 cells. At last, fluorescence microscopy and flow cytometric analysis confirmed the successful uptake of MgAl-LDH/Fe-MOF/D-Man into MDA-MB 231 cell lines, as well as its bioimaging potential. A survey in the published literature approved that this work is the first report on the evaluation of the MgAl-LDH/Fe-MOF/D-Man for targeted co-delivery of both MTX and DOX. Finally, results collectively demonstrate the importance of the biocompatible MgAl-LDH/Fe-MOF/D-Man as a hopeful candidate for biomedicinal applications from the targeted co-drug delivery and bioimaging potential viewpoints.
通常情况下，直接给药的化疗药物在肿瘤治疗中缺乏靶向性。因此，为了提高癌症治疗效率，我们设计了一种新的癌症治疗智能系统。有鉴于此，在本工作中，首先简单地合成了 2-氨基对苯二甲酸（NH-BDC）插层层状双氢氧化物（MgAl-(NH-BDC) LDH）。随后，在存在 MgAl-(NH-BDC) LDH 的情况下，原位生长了基于铁的金属有机骨架（MgAl-LDH/Fe-MOF）。最后，通过 MgAl-LDH/Fe-MOF 与 D-甘露糖（D-Man）的反应，得到了 MgAl-LDH/Fe-MOF/D-Man 三元杂化纳米结构。扫描电子显微镜（SEM）和能谱（EDX）分析证实了在 MgAl-LDH 的存在下形成了具有纳米尺寸的单分散 Fe-MOF。重要的是，MgAl-LDH/Fe-MOF/D-Man 对甲氨蝶呤（MTX）和阿霉素（DOX）的包封效率分别约为 28wt%和 21%。体外药物释放实验表明，在 pH 5.0 时药物释放率更高，而在 pH 7.4 时药物释放率较低，这表明其在抗癌药物输送应用方面具有潜在的应用前景。生物测定结果表明，载药的 MgAl-LDH/Fe-MOF/D-Man 对 MDA-MB 231 细胞具有更高的细胞毒性。最后，荧光显微镜和流式细胞术分析证实了 MgAl-LDH/Fe-MOF/D-Man 成功地被 MDA-MB 231 细胞系摄取，以及其生物成像的潜力。文献综述证实，这是首次报道评估 MgAl-LDH/Fe-MOF/D-Man 对 MTX 和 DOX 联合靶向共递药的研究。最后，结果从靶向共载药和生物成像的潜力两个方面综合证明了生物相容性的 MgAl-LDH/Fe-MOF/D-Man 作为生物医学应用的有希望的候选物的重要性。
