Self‐Destructive Copper Carriers Induce Pyroptosis and Cuproptosis for Efficient Tumor Immunotherapy Against Dormant and Recurrent Tumors

Abstract

Activating the strong immune system is a key initiative to counteract dormant tumors and prevent their recurrence. Herein, self‐destructive and multi‐enzymatically 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. One advantage of this cleverly designed material is that it can disrupt the specific 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 multi‐enzyme activity, it activates NOD‐like receptor protein 3 (NLRP3)‐mediated pyroptosis. Meanwhile, cuproptosis could be triggered by copper ions released from the self‐destructive disintegration of CQG NPs and the sensitivity of cancer cells to cuproptosis was further 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 jointly promote immunosuppressive tumor microenvironment (TME) remodeling, enhance the infiltration of immune cells into the tumor, and subsequently activate robust systemic immunity. Collectively, this study provides a new strategy to better resist tumor dormancy, prevent tumor recurrence, and improve the clinical prognosis of tumors.This article is protected by copyright. All rights reserved

PdCu nanoparticles with multienzymatic activity to treat tumors through the synergistic photothermal and chemodynamic therapy

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Glutathione and acid dual-responsive bismuth-based nanosensitizer for chemo-mediated cancer sonodynamic therapy

“…Rhodamine B (RhB) was loaded in Bi-Bi 2 O 3−x S x to make Bi-Bi 2 O 3−x S x qualify the ability of cell fluorescence imaging [30]. Typically, RhB and Bi-Bi 2 O 3−x S x were stirred for 24 h in dimethyl sulfoxide at a ratio of 1 : 1 in the dark.…”

Cuproptosis: Mechanism, role, and advances in urological malignancies

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