Acid-responsive drug-loaded copper phosphate nanoparticles for tumor cell therapy through synergistic apoptosis and ferroptosis strategy

被引:7
|
作者
Zhao, Sheng [1 ]
He, Liang [1 ]
Sun, Yihao [1 ]
Xu, Ting [1 ]
Chen, Chunmei [1 ]
Ouyang, Yi [1 ]
Chen, Yan [1 ]
Tan, Yixin [1 ]
Zhou, Benqing [2 ]
Liu, Hui [1 ]
机构
[1] Southwest Univ, Sch Mat & Energy, Key Lab Luminescence Anal & Mol Sensing, Minist Educ, Chongqing 400715, Peoples R China
[2] Shantou Univ, Coll Engn, Dept Biomed Engn, Shantou 515063, Peoples R China
关键词
Copper phosphate; Apoptosis; Ferroptosis; Tumor therapy; CANCER; NANOCARRIER; AUTOPHAGY; DELIVERY; DEATH;
D O I
10.1007/s11051-022-05655-5
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Synergistic apoptosis and ferroptosis strategy is quite promising for tumor treatment. Herein, a kind of polyacrylic acid-stabilized, carboxymethyl chitosan-coated, doxorubicin (DOX)-loaded copper phosphate nanoparticles (NPs) were prepared by a simple method for synergistic apoptosis and ferroptosis against tumor cells. The finally formed PAA-Cu-3(PO4)(2)-DOX-CMCS (PCPDC) NPs displayed suitable hydrodynamic size (208.7 nm) and surface charge. When uptaken by tumor cells, they were degraded under acidic circumstances, releasing DOX and Cu2+ ions. The released Cu2+ ions reacted with glutathione (GSH) to produce Cu+ ions and deplete GSH. Through Cu+ ions-mediated Fenton-like reaction, H2O2 can be converted to hydroxyl radical to produce lipid hydroperoxides. Furthermore, the depleted GSH down-regulated the expression of glutathione peroxidase 4 (GPX4) protein, promoting the accumulation of lipid hydroperoxides to enhance ferroptosis. The released DOX can effectively induce apoptosis in tumor cells. These developed Cu-3(PO4)(2)-based nanomaterials can kill tumor cells effectively through the synergistic apoptosis and ferroptosis strategy.
引用
收藏
页数:11
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