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. 2023 Mar 5;634:122675. doi: 10.1016/j.ijpharm.2023.122675. Epub 2023 Feb 1.
Recently, metal-organic frameworks (MOFs) have attracted tremendous attention as promising porous drug delivery systems for cancer treatment. In this work, for the first time, a novel magnetic maltose disaccharide molecule modified with MIL-88 metal-organic framework (FeO@C@MIL-88) was prepared, and then this targeted system was used for the delivery of the doxorubicin (DOX) drug. Eventually, FeO@C@MIL-88-DOX were successfully decorated with folic acid conjugated chitosan (FeO@C@MIL-88-DOX-FC) as a new targeted and controlled release drug system for treatment of MCF-7 breast cancer. The encapsulation efficiency of the DOX in the FeO@C@MIL-88 was obtained at ∼83.6%. The in vitro drug release profiles showed a pH-responsive controlled release of DOX in acidic pH confirming the performance of the systems in the cancerous environment. The DOX release mechanism from systems at pH 5 also showed that the kinetic data well fitted to the Korsmeyer-Peppas and Fickian diffusion. Furthermore, in vitro cytotoxicity and DAPI staining study clearly illustrated that the synthesized FeO@C@MIL-88 system had low cytotoxicity and good biocompatibility against MCF-7 cancer cells and MCF-10A normal cells. Whereas, FeO@C@MIL-88-DOX and FeO@C@MIL-88-DOX-FC exhibited good antitumor activity as a result of targeted delivery of DOX, which indicated the MCF-7 cell death with apoptotic effects. Based on these findings, the resulting carriers could be used as promising targeted drug delivery systems for cancer therapy.
最近,金属-有机骨架(MOFs)作为治疗癌症的有前途的多孔药物传递系统引起了极大的关注。在这项工作中,首次制备了一种新型的磁性麦芽糖二糖分子,并用 MIL-88 金属-有机骨架(FeO@C@MIL-88)进行修饰,然后将该靶向系统用于阿霉素(DOX)药物的传递。最终,成功地用叶酸偶联壳聚糖(FeO@C@MIL-88-DOX-FC)修饰了 FeO@C@MIL-88-DOX,作为一种新的靶向和控制释放药物系统,用于治疗 MCF-7 乳腺癌。在 FeO@C@MIL-88 中 DOX 的包封效率约为 83.6%。体外药物释放曲线表明,在酸性 pH 下,DOX 具有 pH 响应的控制释放性能,证实了该系统在癌变环境中的性能。在 pH 5 下从系统中释放 DOX 的机制也表明,动力学数据很好地符合 Korsmeyer-Peppas 和 Fickian 扩散。此外,体外细胞毒性和 DAPI 染色研究清楚地表明,合成的 FeO@C@MIL-88 系统对 MCF-7 癌细胞和 MCF-10A 正常细胞具有低细胞毒性和良好的生物相容性。然而,FeO@C@MIL-88-DOX 和 FeO@C@MIL-88-DOX-FC 表现出良好的抗肿瘤活性,因为 DOX 的靶向传递,这表明 MCF-7 细胞死亡具有凋亡作用。基于这些发现,所得载体可用作癌症治疗的有前途的靶向药物传递系统。