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

• Published in: Journal of drug delivery science and technology 2021-12, Vol.66, p.102782, Article 102782
• Main Authors: Wang, Dazhuang, Luo, Fuyao, He, Fang, Lu, Feifei, Tao, Xu, Song, Ke, Zhao, Jinghua, Chen, Lijiang
• Format: Article
• Language: English
• Subjects: Apoptosis; Curcumol; Growth inhibition; HepG2 cells; PEG-PCL polymersome
• ISSN: 1773-2247
• DOI: 10.1016/j.jddst.2021.102782

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. [Display omitted] •In this work, we obtained a series of compounds by structural modification of curcumol. After that, we conducted in vitro activity screening of these compounds. The most active compound(curcumol-derivative CD-2e) in vitro was selected for the next study.•We studied the anti-tumor activity of curcumol derivative CD-2e on HepG2 cells, including the effects on HepG2 cell morphology, apoptosis, cell cycle dynamics and protein expression.•We prepared a drug-loaded polymersome-PEG-PCL-CD-2e to further enhance the efficacy of the CD-2e.•We used computer-aided drug design methods to perform molecular dynamics simulations on the state of polymers and drugs to determine the feasibility of the experiment.