1. Multichannel Sonocatalysis Amplifiers Target IDH1-Mutated Tumor Plasticity and Attenuate Ros Tolerance to Repress Malignant Cholangiocarcinoma.
- Author
-
Wang, Duo, Zhu, Xiaoqi, Wang, Xiaobo, Wang, Qin, Yan, Kangning, Zeng, Guichun, Qiu, Guanhua, Jiao, Rong, Lin, Xia, Chen, Jie, Yang, Qiaoling, Qin, Wen, Liu, Junjie, Zhang, Kun, and Liu, Yan
- Subjects
- *
CHOLANGIOCARCINOMA , *ADENOSINE triphosphatase , *ISOCITRATE dehydrogenase , *TUMORS , *ENERGY metabolism , *TRIPTOLIDE - Abstract
Tumor adaptation-originated tumor tolerance that compensatory mechanisms (e.g., isocitrate dehydrogenase (IDH) mutation) jointly shape is the dominant obstacle of ROS therapy. Currently, targeting a single pathway fails to fundamentally reverse the complex milieu and diminish tumor adaptation. Herein, a multichannel sonocatalysis amplifier is engineered via one-pot gas diffusion method to attenuate IDH1-mutated cholangiocarcinoma plasticity and tolerance to ROS therapy, wherein triptolide and IR780 are co-loaded in DSPE-mPEG-modified CaCO3 nanoparticles. Triptolide can blockade Nrf2 to cut off glutathione biosynthesis via blockading proteomic communication, and disrupt redox homeostasis to potentiate IR780-mediated sonocatalytic ROS production. ROS-induced mitochondria damages disrupt Ca2+ homeostasis and in turn aggravate ROS accumulation, which cooperates with sonocatalysis and Nrf2 blockade to reprogram mitochondrial energy and substance metabolism (e.g., adenosine triphosphatase and glutathione), hinder DNA self-repair, and impair IDH1-mutation-asired tolerance. Systematic experiments support that these actions in such multichannel sonocatalysis amplifiers indeed disrupt Ca2+/redox homeostasis to disarm robust tumor plasticity and IDH1-mutation-induced tolerance to sonocatalysis therapy against IDH1-mutated cholangiocarcinoma progression. Briefly, the sonocatalysis amplifiers pave a comprehensive avenue to reprogram tumor metabolism, target tumor vulnerability, and attenuate tumor plasticity against genomic instability-raised treatment adaptation. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF