Introduction: Numerous options for treatment of glioblastoma have been explored; however, single-drug therapies and poor targeting have failed to provide effective drugs. Chemotherapy has significant antitumor effect, but the efficacy of single-drug therapies in the clinic is limited over a long period of time. Thus, novel therapeutic approaches are necessary to address these critical issues.
Objectives: The present study, we investigated a tumor-specific metal-tea polyphenol-based cascade nanoreactor for chemodynamic therapy-enhanced chemotherapy.
Methods: HA-EGCG was synthesized for the first time by introducing epigallocatechin-3-gallate (EGCG) into the skeleton of hyaluronic acid (HA) with reducible disulfide bonds. A rapid and green method was developed to fabricate the metal-tea polyphenol networks (MTP) with an HA-EGCG coating (DOX@MTP/HA-EGCG) based on Fe3+ and EGCG for targeted delivery of doxorubicin hydrochloride (DOX). GL261 cells were used to evaluate the antitumor efficacy of the DOX@MTP/HA-EGCG nanoreactor in vitro and in vivo.
Results: DOX@MTP/HA-EGCG nanoreactors were able to disassemble, resulting in escape of their components from lysosomes and precise release of DOX, Fe3+, and EGCG in the tumor cells. HA-EGCG depleted glutathione to amplify oxidative stress and enhance chemodynamic therapy. The results of in vivo experiments suggested that DOX@MTP/HA-EGCG specifically accumulates at the CD44-overexpressing GL261 tumor sites and that sustained release of DOX and Fe3+ induced a distinct therapeutic outcome.
Conclusions: The findings suggested the developed nanoreactor has promising potential as a future GL261 glioblastoma therapy.
Keywords: Acid/glutathione responsiveness; Chemodynamic therapy; Epigallocatechin-3-gallate; Fenton reaction; Glioblastoma.
© 2021 The Authors. Published by Elsevier B.V. on behalf of Cairo University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).