Putative mechanism for cancer suppression by PLGA nanoparticles loaded with Peganum harmala smoke extract

Abstract

Synthesis and investigation of biological activity of Peganum harmala smoke-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles. Peganum harmala smoke-loaded PLGA nanoparticles (PHSE-PNP) were produced by double emulsion solvent evaporation method and characterised by scanning electron microscopy (SEM), dynamic light scattering (DLS), and ζ-potential. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) for toxicity evaluation, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric reducing antioxidant power (FRAP) assay for antioxidant power, chorioallantoic membrane (CAM), qPCR, and scratch assay for angiogenesis and mouse cancer model for antitumor effects of PHSE-PNP’s were used. PHSE-PNP with a size of 216.33 nm, polydispersity index (PDI): 0.22 and ζ-potential: −25.41 mV inhibited A2780, PC3, A549, HepG2, Mda-mb-231, HT-29 as cancer cells and HUVEC as an normal cells with half-maximal inhibitory concentration (IC₅₀) at about 208.62, 479.05, 1092.6, 1103.9, 1299.21, 3467.5, and <4000 µg/ml, respectively. Also PHSE-PNP inhibited ABTS (IC₅₀: 0.720 mg/ml), DPPH (IC₅₀: 1.36 mg/ml) free radicals and decreased the size of murine tumours (88.3% in 11 days) and suppressed angiogenesis in the CAM and scratch assays. PHSE-PNP can be considered as a potential chemopreventive agent in cancer therapy.

Keywords:

• PLGA-based nanoparticles
• safe cytotoxic impact
• cell-selective anticancer activity
• anti-angiogenic
• antioxidant
• Peganum harmala smoke extract (PHSE)

Acknowledgements

The authors very much appreciate the support provided by the Islamic Azad University, Tehran, Iran, in the conducting of the present research.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The present work was funded by Islamic Azad University, Tehran, Iran. The university’s support of this research is very much appreciated by the authors.