Year-end Sale % OFF 
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 vitro cytotoxicity assay showed that PEG-CD/AD/SF nanoparticles had an approximately 4.7-fold decrease in the IC50 value compared to that of PEG-CD/AD and SF physical mixtures, indicating stronger inhibitory effect against HepG2 cells by co-loading these two drugs. In summary, this novel supramolecular nanosystem provided a simple strategy to co-deliver doxorubicin and sorafenib toward hepatoma cells, which showed promising potential for treatment of HCC.
Highlights
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death
To ensure that the product with only one of the carboxyl groups of DTGA conjugated with Ada was collected, excess DTGA was added during the reaction process and the product was further purified by prep-HPLC
The results suggested that poly (ethylene glycol)-β-cyclodextrin (PEG-CD)/adamantine-terminated doxorubicin prodrug (AD)/SF nanoparticles exert stronger inhibitory effect against HepG2 cells by co-loading DOX and SF into the same nanosystem
Summary
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death The therapeutic efficacy of DOX for HCC is often limited because of the emergence of drug resistance (Deng et al, 2015; Galun et al, 2017) and its irreversible cardiotoxicity (Singal and Iliskovic, 1998). During the clinical application, it was found that SF was only beneficial to about 33% HCC patients while showed low tumor response to other majority of patients (Cheng et al, 2009). Clinical trial studies have demonstrated that combination of DOX with SF exhibited remarkable improvement in the overall survival of HCC patients (Hutchinson, 2011; Pazo Cid et al, 2011)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
