This study explored the synthesis of MIL-68(Al), characterized its properties, and investigated its ability to encapsulate and release melatonin (MEL) in response to changes in pH, intending to develop a more effective drug delivery system. Analyses were directed to characterize the designed nanocarriers before and after drug loading. The drug loading efficiency (DLE) and drug loading content (DLC) of MIL-68(Al) were 78.8% and 44.0%, respectively. The extended drug release period of MEL@MIL-68(Al) was observed to exhibit a faster release under acidic conditions compared to neutral conditions. The cell treatment with free MEL, MIL-68(Al), and MEL@MIL-68(Al) was completed, and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed at lung cancer A549 cells and normal fibroblastic MRC-5 cells for the cytotoxicity study. MEL@MIL-68(Al) was more cytotoxic than MIL-68(Al) in A549 cells. Analyzing reactive oxygen species (ROS) levels via fluorescent microscopic analysis showed ROS overproduction in cells treated with MEL@MIL-68(Al) in comparison to other interventions. Additionally, MEL@MIL-68(Al) modulated the protein expression levels of Nrf-2, Keap-1, and HO-1 in cells. Therefore, MEL@MIL-68(Al) exerts its potent anticancer effects via ROS overproduction and downregulation of the Nrf2/Keap-1 pathway. Therefore, this system can be a promising nanoplatform for the successful delivery of MEL and potentiating its anticancer effects.

中文翻译：

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探索用于褪黑激素递送的 MIL-68(Al) 纳米载体：探索癌细胞中的促氧化作用并实现药物持续释放


本研究探索了 MIL-68(Al) 的合成，表征了其性质，并研究了其响应 pH 变化封装和释放褪黑激素 (MEL) 的能力，旨在开发更有效的药物递送系统。分析旨在表征所设计的纳米载体在载药之前和之后的特征。 MIL-68(Al)的载药效率(DLE)和载药量(DLC)分别为78.8%和44.0%。观察到 MEL@MIL-68(A1) 的延长药物释放期在酸性条件下比中性条件下表现出更快的释放。用游离MEL、MIL-68(A1)和MEL@MIL-68(A1)完成细胞处理，并用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物(MTT) ）对肺癌 A549 细胞和正常成纤维细胞 MRC-5 细胞进行细胞毒性研究。 MEL@MIL-68(A1)在A549细胞中比MIL-68(A1)更具细胞毒性。通过荧光显微镜分析来分析活性氧（ROS）水平表明，与其他干预措施相比，用MEL@MIL-68（A1）处理的细胞中ROS产生过量。此外，MEL@MIL-68(A1)调节细胞中Nrf-2、Keap-1和HO-1的蛋白表达水平。因此，MEL@MIL-68(Al)通过ROS过量产生和Nrf2/Keap-1途径的下调发挥其有效的抗癌作用。因此，该系统可以成为成功传递 MEL 并增强其抗癌作用的有前途的纳米平台。