Targeted Delivery of Doxorubicin to Hepatoma Cells by Lactobionic Acid-Decorated Dual Redox-Responsive Polyethylene Glycol-Doxorubicin Nanoparticles

In this work, we synthesized lactobionic acid-decorated diselenide-linked polyethylene glycol-doxorubicin conjugate (LA-PEG-SeSe-DOX) and prepared free DOX-loaded LA-PEG-SeSe-DOX(DOX@LA-PEG-SeSe-DOX) nanoparticles for hepatoma-targeted DOX delivery. LA-PEG-SeSe-DOX can self-assemble into nanoparticles in deionized water and DOX@LA-PEG-SeSe-DOX nanoparticles were prepared by loading free DOX into LA-PEG-Se-Se-DOX nanoparticles under sonication. DOX@LA-PEG-SeSe-DOX nanoparticles have high DOX loading content of 31.3%. The dynamic scattering analysis shows that DOX@LA-PEG-SeSe-DOX nanoparticles have small size (hydrodynamic diameter 4 5 . 6 9 ± 0 . 7 1 $45.69\pm 0.71$ $$ nm), near neutral zeta potential, and excellent colloidal stability. The in vitro drug release study indicates that DOX@LA-PEG-SeSe-DOX nanoparticles exhibit dual redox-responsive drug release characteristics. The cellular uptake study reveals that DOX@LA-PEG-SeSe-DOX nanoparticles can be taken up by hepatoma cells by asialoglycoprotein receptor (ASGPR)-mediated pathway. Finally, DOX@LA-PEG-SeSe-DOX nanoparticles exhibit enhanced cytotoxicity against HepG2 cells as compared to LA-PEG-SeSe-DOX nanoparticles, underlining the significance of releasing free DOX for effective tumor cell proliferation inhibition. This work provides a facile and effective strategy for targeted delivery of DOX to hepatoma cells.