Affiliation:
1. Department of Gastrointestinal Surgery Guangxi Medical University Cancer Hospital Guangxi Medical University. No. 71 Hedi Road Nanning Guangxi 530021 P. R. China
2. Central Laboratory and Department of Orthopaedics Shanghai Tenth People's Hospital Tongji University School of Medicine Tongji University. No. 301 Yan‐chang‐zhong Road Shanghai 200072 P. R. China
3. Central Laboratory Sichuan Academy of Medical Sciences Sichuan Provincial People's Hospital University of Electronic Science and Technology of China No. 32, West Second Section, First Ring Road Chengdu Sichuan 610072 P. R. China
Abstract
AbstractAbnormal epigenetic regulation is identified to correlate with cancer progression and renders tumor refractory and resistant to reactive oxygen species (ROS)‐based anti‐tumor actions. To address it, a sequential ubiquitination and phosphorylation epigenetics modulation strategy is developed and exemplified by the well‐established Fe‐metal‐organic framework (Fe‐MOF)‐based chemodynamic therapy (CDT) nanoplatforms that load the 26S proteasome inhibitor (i.e., MG132). The encapsulated MG132 can blockade 26S proteasome, terminate ubiquitination, and further inhibit transcription factor phosphorylation (e.g., NF‐κB p65), which can boost pro‐apoptotic or misfolded protein accumulations, disrupt tumor homeostasis, and down‐regulate driving genes expression of metastatic colorectal cancer (mCRC). Contributed by them, Fe‐MOF‐unlocked CDT is magnified to considerably elevate ROS content for repulsing mCRC, especially after combining with macrophage membrane coating‐enabled tropism accumulation. Systematic experiments reveal the mechanism and signaling pathway of such a sequential ubiquitination and phosphorylation epigenetics modulation and explain how it could blockade ubiquitination and phosphorylation to liberate the therapy resistance to ROS and activate NF‐κB‐related acute immune responses. This unprecedented sequential epigenetics modulation lays a solid foundation to magnify oxidative stress and can serve as a general method to enhance other ROS‐based anti‐tumor methods.
Funder
National Natural Science Foundation of China
Fundamental Research Funds for the Central Universities
Subject
General Physics and Astronomy,General Engineering,Biochemistry, Genetics and Molecular Biology (miscellaneous),General Materials Science,General Chemical Engineering,Medicine (miscellaneous)
Cited by
7 articles.
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