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Zhao, Sheng; He, Liang; Sun, Yihao; Xu, Ting; Chen, Chunmei; Ouyang, Yi; Chen, Yan; Tan, Yixin; Zhou, Benqing; Liu, Hui
Journal of nanoparticle research : an interdisciplinary forum for nanoscale science and technology, 2023/1, Volume: 25, Issue: 1Journal Article
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 (PO 4 ) 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 Cu 2+ ions. The released Cu 2+ ions reacted with glutathione (GSH) to produce Cu + ions and deplete GSH. Through Cu + ions-mediated Fenton-like reaction, H 2 O 2 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 (PO 4 ) 2 -based nanomaterials can kill tumor cells effectively through the synergistic apoptosis and ferroptosis strategy.
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