Synthesis and Application of a pH-Responsive Functional Metal-Organic Framework: In Vitro Investigation for Delivery of Oridonin in Cancer Therapy

• Published in: Molecules (Basel, Switzerland) Switzerland), 2024-06, Vol.29 (11), p.2643
• Main Authors: Shen, Jingyi, Gao, Fangxin, Pan, Qian, Zong, Zhihui, Liang, Lili
• Format: Article
• Language: English
• Subjects: A549 Cells; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Bioavailability; Cancer; Cancer therapies; Care and treatment; Cell Line, Tumor; Cell Survival - drug effects; Cytotoxicity; Diterpenes, Kaurane - chemistry; Diterpenes, Kaurane - pharmacology; Drug Carriers - chemistry; drug delivery; Drug Delivery Systems; Drug Liberation; Drugs; Health aspects; Humans; Hydrogen-Ion Concentration; Imidazoles; Ligands; Lung cancer; Medicine, Botanic; Medicine, Herbal; Metal-Organic Frameworks - chemistry; Morphology; nanocarriers; Nanoparticles; Neoplasms - drug therapy; Neoplasms - pathology; oridonin; Particle size; Physiology; Tumors; Vehicles; Zeolites - chemistry; zeolitic imidazolate framework-8
• ISSN: 1420-3049; 1420-3049
• 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.