Controlled drug release using ascorbate-responsive quercetin-conjugated alginate hydrogels

Abstract

In this paper, we report a new strategy for controlled cargo release using quercetin-conjugated alginate (Alg) hydrogels that has enhanced hydrogel stability and can release cargo molecules through on-demand metal cation reduction by a biological reducing agent, ascorbate. By conjugating hydrophobic quercetin to the Alg backbone, hydrogel stability was increased. The encapsulated cargos were released on demand through reduction of cross-linking Fe(III) ions by ascorbate, harnessing the differences in cross-linking capability between Fe(II) and Fe(III). We found that encapsulated fluorescein in quercetin-conjugated Alg hydrogels was released much slower than that in hydrogels without quercetin conjugation. In addition, the stability of the hydrogels and the release of encapsulated fluorescein were controlled by modulating oxidation state of Fe using ascorbate. We validated our strategy by demonstrating the enhanced cancer cell killing of the doxorubicin-encapsulated hydrogels upon treatment with ascorbate. We believe that the strategy would be used as an effective tool for the anticancer drug delivery that can be controlled by ascorbate as overcoming the drawback of Alg hydrogels.