Schiff base bond-linked polysaccharide–doxorubicin conjugate for upregulated cancer therapy

Abstract

The pH-responsive polymer prodrugs were designed to maintain sufficient stability in the bloodstream and promptly release the active drugs when entering the acidic microenvironments, such as tumor tissue and cells. This kind of polymer–drug conjugates has become increasingly intriguing given the specific advantages over traditional drug delivery system. In our work, dextran (Dex) was oxidized into aldehyde-functionalized Dex-CHO before conjugating with doxorubicin (DOX) via efficient Schiff base reaction. The amphiphilic product Dex–DOX aggregated into uniform spherical nanoparticle in aqueous condition. The imine bond in Dex–DOX stayed tough in neutral solution yet quickly fractured when pH was lowered, in which way DOX was locally released and functioned in tumor cells. Our findings proved that the newly-constructed Dex–DOX could obviously promote the pH-dependent drug release, highlight the cell uptake efficiency, and strengthen the antitumor ability toward mouse B16F10 melanoma. In addition, it also largely averted the adverse effects to vital organs, which guaranteed higher level of security. Therefore, Dex–DOX held great potential of becoming a qualified chemotherapeutic drug delivery system.