Nanosized biligated metal–organic framework systems for enhanced cellular and mitochondrial sequential targeting of hepatic carcinoma,Biomaterials Science

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Nanosized biligated metal–organic framework systems for enhanced cellular and mitochondrial sequential targeting of hepatic carcinoma
Biomaterials Science ( IF 5.8 ) Pub Date : 2021-08-16 , DOI: 10.1039/d1bm01247a
Kholoud K Arafa ₁ , Mostafa Fytory ₁ , Shaker A Mousa ₂ , Ibrahim M El-Sherbiny ₁

Affiliation

Mitochondria are reported to play a paramount role in tumorigenesis which positions them as an instrumental druggable target. However, selective drug delivery to cancer-localized mitochondria remains challenging. Herein, we report for the first time, the design, development and evaluation of a hepatic cancer-specific mitochondria-targeted dual ligated nanoscale metal–organic framework (NMOF) for cellular and mitochondrial sequential drug delivery. Surface functionalization was performed through covalent-linking of folic acid and triphenylphosphonium moieties to the aminated Zr-based MOF, NH₂-UiO-66. The characterization of the dual-ligated NMOFs using XRD, FTIR, DSC and BET analysis proved the successful conjugation process. Assessment of the drug loading and release profiling of doxorubicin (DOX)-loaded NMOF confirmed the proper retention of the drug within the NMOF porous structure alongside enhanced release in the tumor acidic environment. Furthermore, biological evaluation of the anti-tumor activity of the DOX-loaded dual-ligated NMOF on hepatocellular carcinoma affirmed the superiority of the developed system in killing the cancerous cells via apoptosis induction and halting cell cycle progression. This study attempts to underscore the promising potential of surface functionalized NMOFs in developing anticancer drug delivery systems to achieve targeted therapy.

中文翻译：

用于增强肝癌细胞和线粒体顺序靶向的纳米双连接金属-有机框架系统

据报道，线粒体在肿瘤发生中起着至关重要的作用，这将它们定位为一种工具性药物靶点。然而，选择性地将药物递送到癌症定位的线粒体仍然具有挑战性。在此，我们首次报告了用于细胞和线粒体顺序给药的肝癌特异性线粒体靶向双连接纳米金属有机框架 (NMOF) 的设计、开发和评估。通过叶酸和三苯基鏻部分与胺化 Zr 基 MOF、NH _{2 的}共价连接进行表面功能化-UiO-66。使用 XRD、FTIR、DSC 和 BET 分析对双连接 NMOF 的表征证明了成功的共轭过程。对载有阿霉素 (DOX) 的 NMOF 的载药量和释放曲线的评估证实了药物在 NMOF 多孔结构内的适当保留，同时在肿瘤酸性环境中增强了释放。此外，对载有 DOX 的双连接 NMOF 对肝细胞癌的抗肿瘤活性的生物学评估证实了所开发的系统在通过诱导凋亡和阻止细胞周期进程杀死癌细胞方面的优越性。本研究试图强调表面功能化 NMOF 在开发抗癌药物递送系统以实现靶向治疗方面的潜力。

更新日期：2021-09-02

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