氧化应激
巨噬细胞
化学
金属
压力(语言学)
癌症研究
放大器
材料科学
生物化学
医学
光电子学
有机化学
CMOS芯片
语言学
哲学
体外
作者
Chu‐Yu Huang,Zhishan Liu,Linping Zhao,Zuxiao Chen,Rongrong Zheng,Xiaona Rao,Yuxuan Wei,Xin Chen,Shiying Li
标识
DOI:10.1016/j.cclet.2024.109696
摘要
The anti-oxidative characteristic and immunosuppressive microenvironment contribute to a high resistance of tumor to many treatments. In this work, a glutathione (GSH)-responsive metal-coordinated oxidative stress amplifier (designated as CuPA) is fabricated to suppress tumor growth through elevating the cellular level of reactive oxygen species (ROS) and eliminating M2 macrophages. Among which, cooper ion (Cu2+) is capable of coordinating with thioredoxin (Trx) inhibitor of PX-12 and signal transducer and activator of transcription 6 (STAT6) inhibitor of AS1517499 with the assistance of distearoyl phosphoethanolamine-PEG2000 (DSPE-PEG2000), which can extensively increase the stability to enhance drug delivery in vitro and in vivo. Furthermore, CuPA can upregulate intracellular ROS to cause tumor cell death through restraining Trx and degrading GSH. Also, CuPA-mediated STAT6 inhibition results in the elimination of M2 macrophage to reverse the immunosuppressive tumor microenvironment. Finally, the elevated oxidative stress and increased immune activation amplify the synergistic antitumor effect without causing obvious side effect. This work provides a new sight for synergistic tumor suppression through chemo-immunotherapy in consideration of the complex resistant tumor microenvironment.
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