光热治疗
化学
体内
过氧化氢
活性氧
纳米技术
材料科学
纳米载体
细胞凋亡
生物物理学
癌细胞
程序性细胞死亡
GPX4
癌症
体外
谷胱甘肽
生物化学
药物输送
谷胱甘肽过氧化物酶
有机化学
生物
酶
生物技术
遗传学
作者
Hongli Yu,Jianqin Yan,Zhipeng Li,Tingting Song,Ning Fang,Jinshan Tan,Yong Sun
摘要
Ferroptosis, a type of programmed cell death induced by the iron-dependent lipid hydroperoxide pathway, has attracted widespread attention. However, Fenton response-dependent ferroptosis has many limitations, such as insufficient reaction conditions in the tumor micro-environment. Here, we propose an all-in-one phototherapy nanoplatform consisting of iron-polydopamine (Fe-PDA), a folic acid-modified red blood cell membrane (FA-RBCm), and epirubicin (EPI), namely, Fe-PDA-EPI@FA-RBCm NPs, to achieve enhanced photothermal-ferroptosis effects via overcoming the limitations of the Fenton-like reaction. The results showed that the synthesized biomimetic nanoparticles could decompose hydrogen peroxide (H2O2) to generate hydroxyl radicals (˙OH), and further induce the non-apoptotic ferroptosis pathway. After irradiation with near-infrared (NIR) light, the uptake of Fe-PDA-EPI@FA-RBCm NPs by cells could be effectively promoted, and it presented impressive in vitro and in vivo photothermal properties. In vitro and in vivo results showed that laser irradiation could enhance ferroptosis by promoting the production of reactive oxygen species (ROS) and lipid peroxides, down-regulating the expression of glutathione peroxidase 4 (GPX4), and reducing the mitochondrial membrane potential. Furthermore, the photothermal-promoted ferroptosis and apoptosis pathways (photothermal therapy and chemotherapy) exhibited outstanding synergistic antitumor efficacy in vitro and in vivo, with an in vivo tumor inhibition rate as high as 76.95%. In conclusion, the construction of tumor-targeted biomimetic nanocarriers utilizing the advantageous properties of RBCm has been investigated as a potential anticancer strategy.
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