Preparation and anti-tumor activity of PEG-PCL polymersomes loaded with curcumol derivative in HepG2 cell line

Curcumol is a natural plant product with anti-tumor properties. However, the clinical application of curcumol is limited by its low water solubility. In this study, we synthesized a curcumol derivative 2e (CD-2e) with improved bioavailability and evaluated its cell growth-regulating activities in human hepatoma HepG2 cells, a liver cancer precursor cell line. Using the clone formation assay, we detected that CD-2e inhibits proliferation and activity of HepG2 cells more effectively than curcumol. Flow cytometry analysis indicated that CD-2e can induce HepG2 cell apoptosis and arrests cell cycle in S phase. Acridine orange-ethidium bromide(AO-EB) double staining indicated that CD-2e triggers HepG2 cell apoptosis in a time-dependent manner. Additionally protein expression analysis showed that CD-2e treatment reduced expression levels of c-Jun N-terminal kinase 1 (JNK1) and its phosphorylated form, P-JNK1. PEG-PCL polymersome carrying CD-2e (PEG-PCL-CD-2e) were generated to improve drug delivery. The prepared PEG-PCL-CD-2e had a uniform particle size distribution, with an average particle size of about 190 nm, and good in vitro stability. The drug release and cell uptake experiments showed that PEG-PCL-CD-2e can rapidly release CD-2e in a weak-acid environment in vitro. Pharmacokinetic studies indicated that, compared with free CD-2e, PEG-PCL-CD-2e enhanced Cmax and Area Under Curve (AUC) (0-∞) by about 1.93-fold and 2.45-fold. The T1/2 was prolonged to 2.59 ± 0.03 h.