Anticancer properties of copolymer nanoparticles loaded with Foeniculum vulgare derivatives in Hs578T and SUM159 cancer cell lines

Abstract

Background: In recent years, the rising occurrence of cancer, particularly breast cancer, has led to a growing interest in utilizing nanotechnology for treatment. As a result of the significant side effects of chemical drugs, researchers have explored the potential of plants with antioxidant properties as an alternative option. Foeniculum vulgare is one of the potent plants for cancer therapy due to its rich anticancer compounds such as anethole, quercetin, kaempferol, and rutin found in its essential oil and ethanolic extract. Methods: This study was conducted to investigate the antitumor properties of F. vulgare, along with the application of copolymers for their targeted delivery to Hs578T and SUM159 cancer cells. First, the ethanolic extract was derived from aerial parts and calluses of F. vulgare through the percolation technique, while the plant’s essential oil extraction was carried out according to the Bettaieb et al method. Second, polymer nanoparticles composed of PLA–chitosan were synthesized, and their characteristics were investigated using various techniques such as Hydrogen nuclear magnetic resonance spectroscopy (1 H-NMR), Fourier transform infrared spectroscopy (FTIR), and thermogravimetric analysis. The preparation of PLA–PEG–HA/PLA–chitosan nanoparticles was accomplished via a solvent diffusion method and the physicochemical properties of these nanoparticles including their size, zeta potential, morphology, size distribution, and magnetic features were evaluated. The encapsulation efficiency of copolymers with F. vulgare ethanolic extract, essential oil, anethole, and pure quercetin was analyzed. After that, the drug release kinetics (at pH = 5 and 7.4), in vitro cytotoxicity evaluation, and analysis of cell apoptosis to evaluate the efficacy of drug delivery to Hs578T and SUM159 triple-negative breast cancer cell lines were evaluated. Results: The results of the study indicated that PLA–PEG–HA/PLA–chitosan nanoparticles possess a spherical shape with an average size of 240 nm and a zeta potential of -10.8 mV. Moreover, the drug release pattern illustrated a higher release rate from synthesized nanoparticles under acidic conditions (pH = 5). The WST-1 assay revealed the biocompatibility of the drug-free nanocarriers and their minimal toxicity. Additionally, the cell apoptosis results indicated a higher proportion of pre- and postapoptotic cells in Hs578T cells compared to SUM-159 cells. Particularly, the Hs578T cell line treated with PLA–PEG–HA/chitosan–PLA/quercetin nanoparticles exhibited the highest percentages of pre- and post-apoptotic cells (34.06% and 8.19%, respectively). Conclusions: The PLA–chitosan and PLA–PEG–HA/chitosan–PLA copolymer nanoparticles exhibit a noteworthy capacity for the targeted delivery of quercetin, anethole, and other anticancer compounds present in the ethanolic extract and essential oil of F. vulgare toward cancerous cells.