Co-embedding of curcumin and gold nanoparticles with ZIF-8 nanoparticles for the treatment of liver cancer and its impact on metabolomics

Abstract

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.

Keywords: Au NPs; Composite drug loaded materials; Cur; Liver cancer; Metabolomics; ZIF-8.