Affiliation:
1. Institute of Molecular Sciences and Engineering Institute of Frontier and Interdisciplinary Science Shandong University Qingdao Shandong 266237 P. R. China
2. Qilu Hospital (Qingdao) Cheeloo College of Medicine Shandong University Qingdao Shandong 266035 P. R. China
Abstract
AbstractActivating the strong immune system is a key initiative to counteract dormant tumors and prevent recurrence. Herein, self‐destructive and multienzymatically active copper‐quinone‐GOx nanoparticles (abbreviated as CQG NPs) have been designed to induce harmonious and balanced pyroptosis and cuproptosis using the “Tai Chi mindset” to awaken the immune response for suppressing dormant and recurrent tumors. This cleverly designed material can disrupt the antioxidant defense mechanism of tumor cells by inhibiting the nuclear factor‐erythroid 2‐related factor 2 (NRF2)‐quinone oxidoreductase 1 (NQO1) signaling pathway. Furthermore, combined with its excellent multienzyme activity, it activates NOD‐like receptor protein 3 (NLRP3)‐mediated pyroptosis. Meanwhile, cuproptosis can be triggered by copper ions released from the self‐destructive disintegration of CQG NPs and the sensitivity of cancer cells to cuproptosis is enhanced through the depletion of endogenous copper chelators via the Michael addition reaction between glutathione (GSH) and quinone ligand, oxygen production from catalase‐like reaction, and starvation‐induced glucose deficiency. More importantly, CQG NPs‐induced pyroptosis and cuproptosis can promote immunosuppressive tumor microenvironment (TME) remodeling, enhance the infiltration of immune cells into the tumor, and activate robust systemic immunity. Collectively, this study provides a new strategy to resist tumor dormancy, prevent tumor recurrence, and improve the clinical prognosis of tumors.
Funder
National Natural Science Foundation of China
China Postdoctoral Science Foundation
Postdoctoral Innovation Project of Shandong Province
Basic and Applied Basic Research Foundation of Guangdong Province
Natural Science Foundation of Shandong Province
Subject
Mechanical Engineering,Mechanics of Materials,General Materials Science
Cited by
3 articles.
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