Glutathione-responsive nanoparticles based on a sodium alginate derivative for selective release of doxorubicin in tumor cells

Abstract

To enhance selective drug release and overcome undesired side effects, novel disulfide crosslinked sodium alginate nanoparticles were designed for achieving glutahione triggered drug release in tumor cells. The doxorubicin loaded crosslinked nanoparticles (DOX-NPs) demonstrated selective drug release in 10 mM glutathione and the further study of their cellular uptake and intracellular release confirmed that the crosslinked nanoparticles could be easily taken up and they only released the encapsulated therapeutic payload in cancer cells. The in vitro cytotoxicity of crosslinked DOX-NPs showed a selective and remarkable cytotoxic effect on Hep-G2 and HeLa cells, instead of on healthy human liver L-O2 cells. More interestingly, the otherwise cardiotoxic DOX showed no cardiotoxicity when formulated as crosslinked DOX-NPs, in an in vivo zebrafish model. This study has demonstrated that the disulfide crosslinked nanoparticle system may provide a promising drug delivery platform for selective drug release in cancer cells with a much improved safety profile.