Functionalized Tumor-Targeting Nanosheets Exhibiting Fe(II) Overloading and GSH Consumption for Ferroptosis Activation in Liver Tumor
Ke Li
Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing, 400044 P. R. China
Search for more papers by this authorKun Xu
Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing, 400044 P. R. China
Search for more papers by this authorYe He
Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing, 400044 P. R. China
Search for more papers by this authorLu Lu
Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing, 400044 P. R. China
Search for more papers by this authorYulan Mao
Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing, 400044 P. R. China
Search for more papers by this authorPengfei Gao
Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing, 400044 P. R. China
Search for more papers by this authorGenhua Liu
Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing, 400044 P. R. China
Search for more papers by this authorJing Wu
Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing, 400044 P. R. China
Search for more papers by this authorYuchen Zhang
School of Life Science, Chongqing University, Chongqing, 400044 P. R. China
Search for more papers by this authorYang Xiang
Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing, 400044 P. R. China
Search for more papers by this authorCorresponding Author
Zhong Luo
School of Life Science, Chongqing University, Chongqing, 400044 P. R. China
E-mail: [email protected]
Search for more papers by this authorCorresponding Author
Kaiyong Cai
Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing, 400044 P. R. China
E-mail: [email protected]
Search for more papers by this authorKe Li
Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing, 400044 P. R. China
Search for more papers by this authorKun Xu
Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing, 400044 P. R. China
Search for more papers by this authorYe He
Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing, 400044 P. R. China
Search for more papers by this authorLu Lu
Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing, 400044 P. R. China
Search for more papers by this authorYulan Mao
Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing, 400044 P. R. China
Search for more papers by this authorPengfei Gao
Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing, 400044 P. R. China
Search for more papers by this authorGenhua Liu
Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing, 400044 P. R. China
Search for more papers by this authorJing Wu
Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing, 400044 P. R. China
Search for more papers by this authorYuchen Zhang
School of Life Science, Chongqing University, Chongqing, 400044 P. R. China
Search for more papers by this authorYang Xiang
Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing, 400044 P. R. China
Search for more papers by this authorCorresponding Author
Zhong Luo
School of Life Science, Chongqing University, Chongqing, 400044 P. R. China
E-mail: [email protected]
Search for more papers by this authorCorresponding Author
Kaiyong Cai
Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing, 400044 P. R. China
E-mail: [email protected]
Search for more papers by this authorAbstract
Liver tumor is difficult to cure for its high degree of malignancy and rapid progression characteristics. Ferroptosis as a new model of inducing cell death is expected to break the treatment bottleneck of liver tumors. Here, a strategy to induce ferroptosis in HepG2 cells with acid-degradable tumor targeted nanosheets Cu-Hemin-PEG-Lactose acid (Cu-Hemin-PEG-LA) is proposed. After highly ingested by HepG2 cells, Cu-Hemin-PEG-LA nanosheets are degraded by weak acid and release Cu(II) and hemin, which consuming intracellular glutathione (GSH) content and increasing the expression of heme oxygenase 1 (HMOX1) protein, respectively. Furthermore, the expression of glutathione peroxidase 4 protein (GPX4) is down-regulated by consumption intracellular GSH content via converting GSH into glutathione oxidized (GSSG), which is named the classical mode. The intracellular Fe2+ content is overloaded by the significant up-regulation of HMOX1 expression, which is denoted as nonclassical mode. The synergistic effect of classical and nonclassical mode increased the intracellular lipid reactive oxide species, induced the occurrence of ferroptosis and up-regulated the expression of BH3 interacting domain death agonist (BID), apoptosis-inducing factor (AIF), and endonuclease G proteins (EndoG). The synergistic strategy demonstrate the excellent ferroptosis induction ability and antitumor efficacy in vivo, which provides great potential for the clinical transformation of ferroptosis.
Conflict of Interest
The authors declare no conflict of interest.
Open Research
Data Availability Statement
Research data are not shared.
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