Self-engineered binary nanoassembly enabling closed-loop glutathione depletion-amplified tumor ferroptosis
文献信息
Jin Lei, Shenwu Zhang, Zehua Wu, Xinxin Sun, Binghong Zhou, Peiqi Huang, Mingzhu Fang, Lin Li, Cong Luo, Zhonggui He
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.
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来源期刊
Biomaterials Science
Biomaterials Science is an international high impact journal exploring the science of biomaterials and their translation towards clinical use. Its scope encompasses new concepts in biomaterials design, studies into the interaction of biomaterials with the body, and the use of materials to answer fundamental biological questions. Papers do not necessarily need to report a new biomaterial but should provide novel insight into the biological applications of the biomaterial. Articles that primarily focus on demonstrating novel materials chemistry and bring a molecular picture to bear on a given material’s suitability as a biomaterial are more suited to our companion journal, Journal of Materials Chemistry B. Biomaterials Science publishes primary research and review-type articles in the following areas: molecular design of biomaterials, including translation of emerging chemistries to biomaterials science of cells and materials at the nanoscale and microscale materials as model systems for stem cell and human biology materials for tissue engineering and regenerative medicine (Nano)materials and (nano)systems for therapeutic delivery interactions at the biointerface biologically inspired and biomimetic materials, including bio-inspired self-assembly systems and cell-inspired synthetic tools next-generation biomaterials tools and methods
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