Facile Fabrication of Reduction-Responsive Supramolecular Nanoassemblies for Co-delivery of Doxorubicin and Sorafenib toward Hepatoma Cells

Frontiers in Pharmacology
Qingqing XiongTianqiang Song

Abstract

Combination of doxorubicin with sorafenib (SF) was reported to be a promising strategy for treating hepatocellular carcinoma (HCC). In this study, we designed a reduction-responsive supramolecular nanosystem based on poly (ethylene glycol)-β-cyclodextrin (PEG-CD) and a disulfide-containing adamantine-terminated doxorubicin prodrug (AD) for efficient co-delivery of doxorubicin and sorafenib. PEG-CD/AD supramolecular amphiphiles were formed through host-guest interaction between cyclodextrin and adamantine moieties, and then self-assembled into regular spherical nanoparticles with a uniform size of 166.4 nm. Flow cytometry analysis and confocal laser scanning microscopy images showed that PEG-CD/AD nanoparticles could be successfully taken up by HepG2 cells and then released doxorubicin into the cell nuclei. Moreover, sorafenib could be facilely encapsulated into the hydrophobic cores to form PEG-CD/AD/SF nanoparticles with a slightly larger size of 186.2 nm. PEG-CD/AD/SF nanoparticles sequentially released sorafenib and doxorubicin in a reduction-response manner.In vitrocytotoxicity assay showed that PEG-CD/AD/SF nanoparticles had an approximately 4.7-fold decrease in the IC50value compared to that of PEG-CD/AD and SF physical m...Continue Reading

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Citations

Aug 1, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Bartłomiej KostTadeusz Biela
Jun 23, 2020·Oxidative Medicine and Cellular Longevity·Wei-Xing MaLiang-Jun Yan
Jul 17, 2021·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Mohamed Fawzi KabilIbrahim M El-Sherbiny

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Methods Mentioned

BETA
nanoprecipitation
dynamic
transmission electron microscopy
flow cytometry
nuclear magnetic resonance
dynamic dialysis

Software Mentioned

GLOBOCAN

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