Polycationic cyclodextrin nanoparticles induce apoptosis and affect antitumoral activity in HepG2 cell line: An evaluation at the molecular level

[Display omitted] •Ayşe Ercan is 1st author in this manuscript responsible for methodology, data curation, analysis and writing/revision of manuscript.•Mustafa Çelebier is equally credited as first author responsible for funding acquisition, methodology and data curation and writing of manuscript.•Selin Öncül is responsible for methodology, visualization and data curation.•Gamze Varan is responsible for conceptualization, data curation, project administration, writing and editing of manuscript.•Engin Koçak is responsible for methodology, visualization and data curation.•Erem Bilensoy is corresponding author and responsible for conceptualization, funding acquisition, methodology, supervision, writing- review and editing. Hepatocellular carcinoma (HCC) is a highly metastatic primary liver cancer generating molecular alterations that end up escaping the apoptotic machinery and conferring multidrug resistance. Targeted medicines with increased and selective cytotoxicity and minimal drug resistance are essential for the treatment of HCC. In this study, a self-assembled polycationic (PC) amphiphilic β-cyclodextrin (βCDC6) nanoparticle formulation was characterized and its efficacy over HCC cell line HepG2 was evaluated in terms of cytotoxicity, apoptotic potential, chemosensitivity and mitochondrial balance utilizing biochemical, gene expression and proteomic approaches without encapsulating an anti-neoplastic agent. Blank PC βCDC6 exerted an anti-proliferative effect on 3D multicellular HepG2 spheroid tumors. These nanoparticles were able to trigger apoptosis proved by caspase 3/7 activity, gene expression and flow cytometry studies. The subjection of PC restored the chemosensitivity of HepG2 cells by suppressing the function of p-glycoprotein. The proteomic studies with Q-TOF LC/MS revealed 73 proteins that are aberrantly encoded after cells were treated with the blank PC. Metabolomic analysis further confirmed the shift in certain biological pathways. Thus, we confirmed that the hepatocellular carcinoma-targeting βCDC6 PC nanoparticles induce apoptosis, lower the rate of cell proliferation, hinder multidrug resistance and they are convenient carriers for eventual therapeutic administrations in HCC patients.