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.

中文翻译：

---

用于胶质母细胞瘤治疗的肿瘤特异性铁配位表没食子儿茶素-3-没食子酸酯级联纳米反应器

介绍

已经探索了多种治疗胶质母细胞瘤的方案；然而，单一药物疗法和靶向性差未能提供有效的药物。化疗具有显着的抗肿瘤作用，但临床上单药治疗长期疗效有限。因此，需要新的治疗方法来解决这些关键问题。

目标

在本研究中，我们研究了一种基于肿瘤特异性金属茶多酚的级联纳米反应器，用于化学动力学疗法增强化疗。

方法

首次通过将表没食子儿茶素-3-没食子酸酯（EGCG）引入具有可还原二硫键的透明质酸（HA）骨架中合成了HA-EGCG。^{开发了一种快速、绿色的方法来制造具有基于Fe 3+}和EGCG的HA-EGCG涂层（DOX@MTP/HA-EGCG）的金属茶多酚网络（MTP），用于盐酸阿霉素（DOX）的靶向递送。利用GL261细胞评价DOX@MTP/HA-EGCG纳米反应器的体外和体内抗肿瘤功效。

结果

DOX@MTP/HA-EGCG 纳米反应器能够分解，导致其成分从溶酶体中逸出，并在肿瘤细胞中精确释放 DOX、Fe ^{3+和 EGCG。}HA-EGCG 消耗谷胱甘肽，以放大氧化应激并增强化学动力学治疗。体内实验结果表明，DOX@MTP/HA-EGCG 在 CD44 过表达的 GL261 肿瘤位点特异性积累，并且 DOX 和 Fe ³⁺的持续释放诱导了独特的治疗结果。

结论

研究结果表明，所开发的纳米反应器作为未来的 GL261 胶质母细胞瘤治疗具有广阔的潜力。