In vitro pro-apoptotic and anti-metastatic potentials of harmaline-silver containing folate-linked chitosan nano-drug delivery system

Objective(s): Harmaline and green-synthesized silver nanoparticles were encapsulated by folate-linked chitosan molecules as a receptor-mediated drug delivery system to evaluate its pro-apoptotic and anti-metastatic potentials on human ovarian (A۲۷۸۰) and epithelioid (PANC) cancer cells.Materials and Methods: The Ag nanoparticles (AgNP) were synthesized utilizing an herbal bio-platform (Bistorta officinalis) and embedded with harmalin. The Harmaline-ag containing folate-linked chitosan nanoparticles (HA-fCNP) were synthesized utilizing the ionic gelation method. Both the AgNP and HA-fCNP nanoparticles were characterized by DLS, FESEM, and Zeta potential analysis. Moreover, the chemical properties of HA-fCNP and the crystallinity of AgNPs were determined by applying FTIR and XRD methods, respectively. The HA-fCNP cytotoxicity was analyzed on A۲۷۸۰, PANC, and HFF cell lines. Moreover, pro-apoptotic and anti-metastatic potentials of HA-fCNP were studied by analyzing the BAX-BCL۲ and MMP۲-MMP۹ gene expression profiles, respectively. The A۲۷۸۰ cellular death was determined by AO/PI and flow cytometry methods. Results: The HA-fCNP significantly exhibited a selective cytotoxic impact on A۲۷۸۰ and PANC cancerous cell lines compared with normal human foreskin fibroblast (HFF) cells. The increased SubG۱-arrested A۲۷۸۰ cells and up-regulated BAX gene expression following the increased treatment concentrations of hA-fCNP indicated its selective pro-apoptotic activity on A۲۷۸۰ cells. Also, the notable down-regulated expressions of MMP۲ and MMP۹ metastatic genes following the increasing doses of HA-fCNP treatment on A۲۷۸۰ cells confirmed its anti-metastatic activity.Conclusion: The cancer-selective cytotoxicity, apoptotic, and anti-metastatic properties of HA-fCNP are considered the appropriate properties of an anticancer compound.

Keywords:

Anti-metastatic activity , Apoptotic activity , Cancer-selective-cytotoxicity , Harmaline-ag containing- folate-linked chitosan-nanoparticles (HA-fCNP)