Human serum albumin microspheres synchronously loaded with ZIF-8 and triptolide (TP) for the treatment of intrahepatic cholangiocarcinoma.

Abstract

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver tumor and remains a fatal malignancy in most patients. Only 20% to 30% of patients can be treated with potentially curative surgical resection. Local therapies such as radioembolization and hepatic arterial perfusion may be a more effective treatment strategy. The active ingredients of natural plants have aroused wide interest in the treatment of tumors. Triptolide shows toxic effects on a variety of epithelioid carcinoma cells. However, there is currently a lack of suitable delivery system for the treatment of ICC. In this study, organometallic framework material ZIF-8 was chosen to load TP, and then encapsuled in HSA micro-nanoparticles for the perfusion treatment of ICC. The results of SEM, XRD, and FTIR showed that ZIF-8 nanoparticles were encapsuled in HSA micro-nanoparticles. ZIF-8 nanoparticles (57.89 ± 12.24%) and TP@ZIF-8/HSA (36.8 ± 4.71%) micro-nanoparticles could significantly inhibited proliferation of RBE cell. Also, TP@ZIF-8/HSA micro-nanoparticles of all groups exhibited favorable cytocompatibility to L929 cells and hemocompatibility. RT-qPCR and western blot showed that ZIF-8 and TP induced apoptosis in cancer cells through mitochondria-related pathways. The results demonstrated that TP@ZIF-8/HSA was a potential chemotherapy candidate for the treatment of ICC.