Kazemi Amir, Aghamirza Moghim Aliabadi Hooman, Afshari Mohammad Hossein, Tamtaji Mohsen, Baesmat Hasan, Keshavarz Saber, Zeinali Fateme, Torabi Elahe, Ferdowsi Ghodsiyeh Sadat, Manteghi Faranak, Rohani Sohrab, Goddard William A
Research Laboratory of Inorganic Chemistry and Environment, Department of Chemistry, Iran University of Science and Technology, Tehran 16846-13114, Iran.
Department of Chemical and Biochemical Engineering, Western University, London, Ontario N6A 5B9, Canada.
ACS Appl Bio Mater. 2025 Sep 15;8(9):7830-7841. doi: 10.1021/acsabm.5c00838. Epub 2025 Aug 19.
Metal-organic frameworks (MOFs) have emerged as promising nanocarriers for targeted drug delivery, particularly in cancer therapy. Introducing structural defects into MOFs significantly enhances their drug-loading capacity and release efficiency. This study explores porosity modification through defect-engineered MOF-808 nanocarriers, synthesized via a mixed-ligand strategy, to enhance the stability, pH-responsiveness, and drug delivery efficiency for cancer therapy. The modified MOF-808 variants were loaded with 5-fluorouracil (5-FU) in ethanol and water to optimize the drug loading capacity (DLC) and drug release efficiency (DLE). Among them, MOF-808-15% demonstrated a drug release of 57.7% at pH 7.4 and 70.8% at pH 5.5, showing a 22.7% increase under acidic conditions, which is ideal for pH-responsive drug delivery. Density functional theory (DFT) calculations revealed a strong adsorption energy (-1.13 eV) between MOF-808 and 5-FU, confirming effective drug-framework interactions. Additionally, a biodegradable polydopamine (PDA) coating enhanced the stability and enabled controlled drug release in acidic environments. In the 5-FU@MOF-808-15%/PDA system, 64.4% of the drug was released at pH 5.5, marking a 21.97% improvement compared with neutral conditions. Cytotoxicity assays on MCF-7 cells showed 77.65% inhibition, comparable to free 5-FU (80.4%) at 400 μg/mL. These findings demonstrate that precise defect engineering in MOFs can yield highly efficient and biocompatible drug nanocarriers, paving the way for advanced controlled-release cancer therapies.
金属有机框架材料（MOFs）已成为用于靶向给药的有前景的纳米载体，尤其是在癌症治疗方面。将结构缺陷引入MOFs可显著提高其载药能力和释放效率。本研究探索通过混合配体策略合成的缺陷工程化MOF-808纳米载体进行孔隙率修饰，以提高用于癌症治疗的稳定性、pH响应性和药物递送效率。在乙醇和水中用5-氟尿嘧啶（5-FU）负载修饰后的MOF-808变体，以优化载药能力（DLC）和药物释放效率（DLE）。其中，MOF-808-15%在pH 7.4时药物释放率为57.7%，在pH 5.5时为70.8%，在酸性条件下增加了22.7%，这对于pH响应性药物递送来说是理想的。密度泛函理论（DFT）计算表明MOF-808与5-FU之间具有很强的吸附能（-1.13 eV），证实了药物与框架之间有效的相互作用。此外，可生物降解的聚多巴胺（PDA）涂层提高了稳定性，并能在酸性环境中实现药物的控释。在5-FU@MOF-808-15%/PDA系统中，在pH 5.5时64.4%的药物被释放，与中性条件相比提高了21.97%。对MCF-7细胞的细胞毒性试验显示抑制率为77.65%，与400μg/mL的游离5-FU（80.4%）相当。这些发现表明，对MOFs进行精确的缺陷工程可以产生高效且生物相容的药物纳米载体，为先进的控释癌症治疗铺平道路。
