Yu Zhang, Xiyou Du, Xi Gao, Qixiang Feng, Zhijing He, Luyue Wang, He Zhou, Qiaoying Hu, Chunyan Wu, Weilin Wang, Yujuan Chen, Lei Ye, Guoliang Lu, Jianbo Ji, Yanwei Xi, Xiaoye Yang, Guangxi Zhai
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引用次数: 0
Abstract
Accumulating evidence suggests that cupreous nanomaterials are capable to trigger the cuproptosis and ferroptosis of malignant cells, providing possibilities for cancer therapy. However, how to realize synchronous cuproptosis and ferroptosis sensitization remains a research gap. Considering the interplays between cuproptotic and ferroptotic pathways, the manipulation of their common regulators provides a feasible approach; based on this, we innovatively propose a metabolic intervention strategy to synchronously reinforce tumor cells’ cuproptosis/ferroptosis susceptibility. STF-31 is utilized to inhibit glycolysis and compensatory nicotinamide adenine dinucleotide (NAD+) metabolism, which is encapsulated in the lipid bilayers of a composited copper (Cu)-tannic acid (TA) network/liposome system. The as-prepared nanosystem (SCu/L) significantly decreases intracellular glucose, NAD+, reduced nicotinamide adenine dinucleotide phosphate (NADPH) and adenosine triphosphate (ATP) levels and inhibits Cu-ATPase activity, thus inhibiting GSH synthesis and Cu efflux and eventually reinforcing both cuproptosis and ferroptosis. Besides, the glycolysis inhibition effect also helps to remodulate tumor immune microenvironment (TIME), finally boosting anti-tumor immunity together with immunogenic cell death (ICD)-activated T cell immunity. Taken together, this work presents a simple yet effective metabolic intervention strategy for synchronously sensitizing tumor cells to cuproptosis and ferroptosis induced by a cupreous system, providing a feasible pattern for reinforcing the tumoricidal efficiency of cupreous formulations and expanding the prospective applications of ferroptosis/cuproptosis-based therapy.
期刊介绍:
The Chemical Engineering Journal is an international research journal that invites contributions of original and novel fundamental research. It aims to provide an international platform for presenting original fundamental research, interpretative reviews, and discussions on new developments in chemical engineering. The journal welcomes papers that describe novel theory and its practical application, as well as those that demonstrate the transfer of techniques from other disciplines. It also welcomes reports on carefully conducted experimental work that is soundly interpreted. The main focus of the journal is on original and rigorous research results that have broad significance. The Catalysis section within the Chemical Engineering Journal focuses specifically on Experimental and Theoretical studies in the fields of heterogeneous catalysis, molecular catalysis, and biocatalysis. These studies have industrial impact on various sectors such as chemicals, energy, materials, foods, healthcare, and environmental protection.