A Tumor-Specific Ferric-Coordinated Epigallocatechin-3-gallate cascade nanoreactor for glioblastoma therapy
Min Mu, Haifeng Chen, Rangrang Fan, Yuelong Wang, Xin Tang, Mei Lan, Na Zhao, Bingwen Zou, Aiping Tong, Jianguo Xu, Bo Han, Gang Guo
Abstract
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. The present study, we investigated a tumor-specific metal-tea polyphenol-based cascade nanoreactor for chemodynamic therapy-enhanced chemotherapy. 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 ([email protected]/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 [email protected]/HA-EGCG nanoreactor in vitro and in vivo. [email protected]/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 [email protected]/HA-EGCG specifically accumulates at the CD44-overexpressing GL261 tumor sites and that sustained release of DOX and Fe3+ induced a distinct therapeutic outcome. The findings suggested the developed nanoreactor has promising potential as a future GL261 glioblastoma therapy.