Self-engineered binary nanoassembly enabling closed-loop glutathione depletion-amplified tumor ferroptosis

作者全名："Lei, Jin; Zhang, Shenwu; Wu, Zehua; Sun, Xinxin; Zhou, Binghong; Huang, Peiqi; Fang, Mingzhu; Li, Lin; Luo, Cong; He, Zhonggui"

作者地址："[Lei, Jin; Zhang, Shenwu; Wu, Zehua; Sun, Xinxin; Zhou, Binghong; Huang, Peiqi; Fang, Mingzhu; Luo, Cong; He, Zhonggui] Shenyang Pharmaceut Univ, Wuya Coll Innovat, Dept Pharmaceut, Shenyang 110016, Peoples R China; [Li, Lin] Chongqing Med Univ, Dept Pharm, Women & Childrens Hosp, Chongqing Hlth Ctr Women & Children, Chongqing 401147, Peoples R China"

通信作者："Luo, C; He, ZG (通讯作者)，Shenyang Pharmaceut Univ, Wuya Coll Innovat, Dept Pharmaceut, Shenyang 110016, Peoples R China.; Li, L (通讯作者)，Chongqing Med Univ, Dept Pharm, Women & Childrens Hosp, Chongqing Hlth Ctr Women & Children, Chongqing 401147, Peoples R China."

来源：BIOMATERIALS SCIENCE

ESI学科分类：MATERIALS SCIENCE

WOS号：WOS:001092960900001

JCR分区：Q1

影响因子：5.8

年份：2023

卷号：11

期号：22

开始页：7373

结束页：7386

文献类型：Article

关键词：　

摘要："Ferroptosis has emerged as a promising target for anticancer treatment, comprising iron-dependent lipid peroxidation and excessive accumulation of reactive oxygen species. Given that glutathione (GSH) overproduced in tumor cells antagonizes the cellular oxidation system, the reduction of GSH production has been extensively explored to induce ferroptosis. However, reducing GSH production alone is insufficient to trigger an intense lipid peroxidation storm. It is highly desirable to achieve systemic GSH depletion through simultaneous production and consumption intervention. Herein, we propose a bidirectional blockage strategy for closed-loop GSH depletion-amplified tumor ferroptosis. Sorafenib (Sor) and gambogic acid (GA) were elaborately fabricated as a self-engineered carrier-free nanoassembly without any nanocarrier materials. The PEGylated dual-drug nanoassembly enables favorable co-delivery and tumor-specific release of Sor and GA. Notably, a closed-loop GSH depletion is observed as a result of a Sor-induced decrease in GSH production and GA-accelerated GSH consumption in vitro and in vivo. As expected, this uniquely engineered dual-drug nanoassembly demonstrates vigorous antitumor activity in 4T1 breast tumor-bearing mice. This study presents a novel nanotherapeutic modality for ferroptosis-driven cancer treatment. Schematic illustration of a self-engineered dual-drug (GA and Sor) nanoassembly for closed-loop GSH depletion-amplified tumor ferroptosis."

基金机构：This work was financially supported by the National Natural Science Foundation of China (No. 82161138029 and 82204317) and the Natural Science Foundation of Liaoning Province (No. 2022-BS-162).

基金资助正文：This work was financially supported by the National Natural Science Foundation of China (No. 82161138029 and 82204317) and the Natural Science Foundation of Liaoning Province (No. 2022-BS-162).