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Polycationic cyclodextrin nanoparticles induce apoptosis and affect antitumoral activity in HepG2 cell line: An
Ayse Ercan1, Mustafa Çelebier2, Selin Oncul1
1Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, 06100 Ankara Turkey.
Abstract:
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.
Insights
Novel polycationic β-cyclodextrin nanoparticles show potential against hepatocellular carcinoma (HCC). These blank nanoparticles induce apoptosis, reduce proliferation, and overcome drug resistance in HCC cells, offering a promising therapeutic strategy.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Hepatocellular carcinoma (HCC) is a deadly liver cancer characterized by metastasis, apoptosis evasion, and multidrug resistance.
- Effective targeted therapies with minimal resistance are crucial for HCC treatment.
Purpose of the Study:
- To evaluate the efficacy of blank polycationic (PC) amphiphilic β-cyclodextrin (βCDC6) nanoparticles against the HCC cell line HepG2.
- To assess the nanoparticles' impact on cytotoxicity, apoptosis, chemosensitivity, and mitochondrial balance.
Main Methods:
- Utilized biochemical, gene expression, proteomic (Q-TOF LC/MS), and metabolomic analyses.
- Evaluated effects on 3D multicellular HepG2 spheroid tumors.
- Assessed caspase 3/7 activity, p-glycoprotein function, and flow cytometry for apoptosis.
Main Results:
- Blank PC βCDC6 nanoparticles demonstrated anti-proliferative effects on HepG2 spheroids.
- Induced apoptosis, confirmed by caspase activity, gene expression, and flow cytometry.
- Restored chemosensitivity by suppressing p-glycoprotein and altered protein expression and metabolic pathways.
Conclusions:
- Hepatocellular carcinoma-targeting βCDC6 PC nanoparticles effectively induce apoptosis and inhibit proliferation.
- These nanoparticles overcome multidrug resistance in HCC.
- They serve as viable carriers for future therapeutic applications in HCC treatment.
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