Abstract
BACKGROUND: Anaplastic thyroid carcinoma (ATC) is highly malignant with a poor prognosis. Current treatment methods fail to prolong patients' survival periods, and there is an urgent need to explore new strategies. EZH2 is highly expressed in ATC, and its inhibitors EPZ6438 and GSK343 have anti-cancer potential. However, issues such as insufficient drug concentration at the tumor site, drug resistance, and toxic side effects exist. Bovine serum albumin-chitosan nanoparticles have good biocompatibility, can be slowly degraded, continuously release drugs, and enable targeted drug delivery. This study used bovine serum albumin and chitosan as raw materials to prepare nano-delivery devices loaded with GSK343 and EPZ6438, providing new ideas for clinical treatment. METHODS: Two types of nanoparticles were constructed using self-assembly technology, and their characterization and drug release rates were verified. The blood compatibility, in vitro uptake, and effects on the proliferation and apoptosis of ATC cells of the nanoparticles were detected through multiple experiments. Model mice were constructed to explore the in vivo targeting and anti-tumor activity of the nanoparticles and evaluate their biosafety and effectiveness. RESULTS: Two types of nanoparticles were successfully prepared with good characterization, high drug loading capacity, and encapsulation efficiency, and exhibited a sustained-release effect. In vitro experiments showed that the drug-loaded nanoparticles could induce cancer cell apoptosis and inhibit migration and invasion. In vivo studies confirmed that the nanoparticles could inhibit cell metastasis and had excellent biosafety. CONCLUSIONS: Two types of nanoparticles were successfully constructed with good sustained-release, targeting effects, and biosafety. They could improve the therapeutic efficacy and reduce toxic side effects, with GSK343-BSA@CS showing significant effects.