Ceramide-Graphene Oxide Nanoparticles Enhance Cytotoxicity and Decrease HCC Xenograft Development: A Novel Approach for Targeted Cancer Therapy

Frontiers in Pharmacology
Shi-Bing WangXiao-Zhou Mou

Abstract

Despite substantial efforts to develop novel therapeutic strategies for treating hepatocellular carcinoma (HCC), the effectiveness and specificity of available drugs still require further improvement. Previous work has shown that exogenous ceramide can play a key role in inducing the apoptotic death of cancer cells, however, the poor water-solubility of this compound has hampered its use for cancer treatment. In the present study, we used polyethylene glycol (PEG) and polyethylenimine (PEI) co-conjugated ultra-small nano-GO (NGO-PEG-PEI) loaded with C6-ceramide (NGO-PEG-PEI/Cer) as a strategy for HCC treatment. We assessed the biological role of NGO-PEG-PEI/Cer, and we assessed its antitumor efficacy against HCC both in vitro and in vivo in combination with the chemotherapeutic drug sorafenib. We found that NGO-PEG-PEI significantly enhanced the cellular uptake of C6-ceramide. By investigating the mechanism of cellular delivery, we determined that the internalization of NGO-PEG-PEI/Cer progressed primarily via a clathrin-mediated mechanism. The combination of NGO-PEG-PEI/Cer and sorafenib exhibited synergy between these two drugs. Further work revealed that NGO-PEG-PEI/Cer may play a role in subverting multidrug resistance (MDR...Continue Reading

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Citations

Apr 5, 2020·International Journal of Molecular Sciences·Milena GeorgievaNatalia Krasteva
May 6, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Manuela CurcioGiuseppe Cirillo
Sep 8, 2019·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Teodora Alexa-StratulatChiara Riganti
Jun 3, 2021·International Journal of Molecular Sciences·Elisabeth M HaberlChrista Buechler
Jun 29, 2021·Frontiers in Bioengineering and Biotechnology·Julia DriscollTushar Patel
Sep 1, 2021·Biomolecules & Therapeutics·Jinwon ParkYu-Kyoung Oh

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Methods Mentioned

BETA
xenograft
transfection
dynamic laser scattering
flow cytometry
confocal microscopy
fluorescence
xenografts

Software Mentioned

CalcuSyn
SPSS
Statistical Package for the Social Sciences

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