Department of Pharmaceutical Engineering, Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical University, Donghai Avenue, Bengbu 233030, China.
Molecules. 2024 Jun 4;29(11):2643. doi: 10.3390/molecules29112643.
Oridonin (Ori) is a naturally existing diterpenoid substance that mainly exists in the Chinese medicinal plant Rabdosia rubescens. It was previously found to possess intriguing biological properties; however, the quick clearance from plasma and limited solubility in water restricts its use as a drug. Several metal-organic frameworks (MOFs), having big surfaces and large pores, have recently been considered promising drug transporters. The zeolitic imidazolate framework-8 (ZIF-8), a form of MOF consisting of 2-methylimidazole with zinc ions, is structurally stable under physiologically neutral conditions, while it can degrade at low pH values such as in tumor cells. Herein, a nanosized drug delivery system, Ori@ZIF-8, was successfully designed for encapsulating and transporting oridonin to the tumor site. The drug loading of the prepared Ori@ZIF-8 was 26.78%, and the particles' mean size was 240.5 nm. In vitro, the release of Ori@ZIF-8 exhibited acid sensitivity, with a slow release under neutral conditions and rapid release of the drug under weakly acidic conditions. According to the in vitro anti-tumor experiments, Ori@ZIF-8 produced higher cytotoxicity than free Ori and induced apoptosis in A549 cancer cells. In conclusion, Ori@ZIF-8 could be a potential pH-responsive carrier to accurately release more oridonins at the tumor site.
冬凌草甲素（Ori）是一种天然存在的二萜类物质，主要存在于中国药用植物冬凌草中。它以前被发现具有有趣的生物特性；然而，其在血浆中的快速清除和有限的水溶性限制了其作为药物的应用。几种金属有机骨架（MOFs），具有大的表面积和大的孔隙，最近被认为是有前途的药物转运体。沸石咪唑酯骨架-8（ZIF-8）是一种由 2-甲基咪唑和锌离子组成的 MOF，在生理中性条件下结构稳定，而在肿瘤细胞等低 pH 值下可以降解。在此，成功设计了一种纳米药物递送系统 Ori@ZIF-8，用于封装和将冬凌草甲素运输到肿瘤部位。制备的 Ori@ZIF-8 的载药量为 26.78%，颗粒的平均粒径为 240.5nm。在体外，Ori@ZIF-8 的释放表现出酸敏感性，在中性条件下释放缓慢，在弱酸性条件下药物迅速释放。根据体外抗肿瘤实验，Ori@ZIF-8 比游离 Ori 产生更高的细胞毒性，并诱导 A549 癌细胞凋亡。总之，Ori@ZIF-8 可以作为一种潜在的 pH 响应载体，在肿瘤部位更准确地释放更多的冬凌草甲素。
