Wang Xiaohui, Zhou Lin, Shi Yingying, Wang Wang, Li Peng, Cui Rui, Wu Yajuan, Wang Feng, Du Qiuzheng
Department of Ultrasound, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Department of Interventional Therapy, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116000, China.
Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Eur J Pharm Biopharm. 2025 Sep;214:114773. doi: 10.1016/j.ejpb.2025.114773. Epub 2025 Jun 6.
The mortality rate of primary liver malignant tumors is very high. Curcumin (Cur) is one of the most commonly used drugs for the treatment of liver cancer. However, due to its low bioavailability, nano-drug delivery systems are rapidly developing. Zeolitic imidazolate framework-8 (ZIF-8), is pH-sensitive and biodegradable in acidic environments, providing a very suitable platform for drug delivery. Here, the anti-tumor properties of Cur and the anti-inflammatory properties of gold nanoparticles (Au NPs) were integrated and encapsulated in ZIF-8 material to prepare a composite drug delivery system (Cur/Au@ZIF-8). The prepared materials were characterized by scanning electron microscopy and elemental analysis, transmission electron microscopy, and powder X-ray diffraction. The drug loading efficiency of Cur in this delivery system reached 47.16 %. The drug release curve showed that the release rate of Cur/Au@ZIF-8 was faster at pH 5.5, with a release rate of 72.34 %. Ultrasound-guided in situ liver cancer models were constructed in SD rats to investigate the in vivo anti-tumor effects of Cur/Au@ZIF-8 and its impact on the metabolomics of tumor-bearing rats before and after treatment. In vivo results indicated that Cur/Au@ZIF-8 showed better anti-tumor effects, with a tumor inhibition rate of 46.81 %. After treatment, 26 key differential metabolites (p < 0.05) were identified from expression patterns and metabolic pathways, which were mainly related to fatty acid metabolism. This treatment strategy provides a reference for future cancer treatment and mechanism exploration.
原发性肝恶性肿瘤的死亡率非常高。姜黄素（Cur）是治疗肝癌最常用的药物之一。然而，由于其生物利用度低，纳米药物递送系统正在迅速发展。沸石咪唑酯骨架-8（ZIF-8）对pH敏感，在酸性环境中可生物降解，为药物递送提供了一个非常合适的平台。在此，将Cur的抗肿瘤特性和金纳米颗粒（Au NPs）的抗炎特性整合并封装在ZIF-8材料中，制备了一种复合药物递送系统（Cur/Au@ZIF-8）。通过扫描电子显微镜、元素分析、透射电子显微镜和粉末X射线衍射对制备的材料进行了表征。Cur在该递送系统中的载药效率达到47.16%。药物释放曲线表明，Cur/Au@ZIF-8在pH 5.5时释放速率更快，释放率为72.34%。在SD大鼠中构建超声引导原位肝癌模型，以研究Cur/Au@ZIF-8的体内抗肿瘤作用及其对荷瘤大鼠治疗前后代谢组学的影响。体内结果表明，Cur/Au@ZIF-8显示出更好的抗肿瘤效果，肿瘤抑制率为46.81%。治疗后，从表达模式和代谢途径中鉴定出26种关键差异代谢物（p<0.05），主要与脂肪酸代谢有关。该治疗策略为未来癌症治疗和机制探索提供了参考。
