Abstract
Galactose-modified selenium nanoparticles (GA-SeNPs) loading with doxorubicin (DOX) for hepatocellular carcinoma (HCC) therapy was investigated in this paper. Selenium nanoparticles (SeNPs) were modified with galactose as tumor targeting moiety to fabricate tumor-targeted delivery carrier GA-SeNPs, then doxorubicin was loaded onto the surface of GA-SeNPs for improving antitumor efficacy of DOX in HCC therapy. Chemical structure characterization of GA-Se@DOX showed that DOX was successfully loaded to the surface of GA-SeNPs to prepare functionalized antitumor drug delivery system GA-Se@DOX. GA-Se@DOX exhibited effective cellular uptake in HepG2 cells and entered HepG2 cells mainly by clathrin-mediated endocytosis pathway. GA-Se@DOX showed significant activity to induce the apoptosis of HepG2 cells in vitro. The western blotting result indicated that GA-Se@DOX induced HepG2 cells apoptosis via activating caspase signaling and Bcl-2 family proteins. Moreover, active targeting delivery system GA-Se@DOX exhibited excellent antitumor efficacy in vivo in comparison with passive targeting delivery system Se@DOX. Histology analysis showed that GA-Se@DOX exhibited no obvious damage to major organs including heart, liver, spleen, lung, and kidney under the experimental condition. Taken together, GA-Se@DOX may be one novel promising nanoscale drug candidate for HCC therapy.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common lethal diseases worldwide (Hu et al, 2015; Jha et al, 2017)
1 mL 2 mg/mL galactose was dropped to Selenium nanoparticles (SeNPs) solution and mixed solutions were magnetically stirred for 4 h to fabricate GA-modified selenium nanoparticles (GASeNPs)
Obvious signals of carbon atom, oxygen atom, and selenium atom were observed in energy dispersive X-ray (EDX) analysis, indicating that GA and DOX were linked to the surface of SeNPs (Figure 2(B))
Summary
Hepatocellular carcinoma (HCC) is one of the most common lethal diseases worldwide (Hu et al, 2015; Jha et al, 2017). Doxorubicin (DOX) is one very common and effective chemotherapeutic drugs for cancer therapy (Bi et al, 2018; Licciardello et al, 2018). Uncontrolled release of drug and drug delivery to the unintended site may compromise treatment effect along with increased risk of toxicity and side effect (Le et al, 2015; Sun et al, 2018b). These side effects can be minimized by using controlled targeted drug delivery, such as nanocarriers (Li et al, 2017a; Kim et al, 2018)
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