期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 598, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ijpharm.2021.120379
关键词
Apoptosis; Cyclodextrin; Drug resistance; Hepatocellular carcinoma, nanoparticle; Proteomics
资金
- Scientific and Technological Research Council of Turkey (TUBITAK) [:115S456]
- Spanish Ministry of Science and Innovation [RTI2018-097609-BC21]
This study highlights the potential of novel nanoparticles for treating hepatocellular carcinoma by inhibiting cell proliferation, inducing apoptosis, and reducing multidrug resistance. Blank nanoparticles were able to restore chemosensitivity in HCC cells.
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 beta-cyclodextrin (beta CDC6) 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 beta CDC6 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 carcinomatargeting beta CDC6 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.
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