Work

Tumor microenvironment activated MXene-protected Cu2O heterojunctions induce tumor-specific cuproptosis for enhanced sono-immunotherapy

Year: 2024

Type: article

Abstract: The utilization of a copper ionophore to induce programmed cell death, known as cuproptosis, shows potential in augmenting the efficacy of traditional anticancer treatments and eliciting robust adaptive immune responses. Nevertheless, the non-tumor-specific release of Cu ions may initiate cuproptosis and cause irreversible damage to normal tissues. Herein, this work reports for the first time the regulation of degradation behaviors of Cu-based nanomaterials using Ti 3 C 2 T x nanosheets as a protection layer to maximize the therapeutic effects of tumor-specific cuproptosis. A Z-scheme heterojunction termed Cu 2 O/Ti 3 C 2 T x is facilely constructed by coating Ti 3 C 2 T x nanosheets on the surface of Cu 2 O nanocubes. The fabrication of heterojunctions not only improves the sonodynamic and chemodynamic activities of Cu 2 O nanocubes owing to the manipulation of electron-hole transfer process, but also avoids the degradation of Cu 2 O nanocubes under normal physiological conditions. The tumor-specific released Cu ions not only realized the cascade amplification of ROS generation through Cu + -mediated Fenton-like reaction and Cu 2+ -facilitated GSH depletion, but also triggered cuproptosis through Cu + -induced DLAT oligomerization and mitochondrial dysfunction. More importantly, the immunosuppressive TME could be reversed by the greatly enhanced ROS levels and high-efficiency cuproptosis, ultimately inducing immunogenic cell death that promotes robust systemic immune responses for the eradication of primary tumors and suppression of distant tumors. This work provides a promising perspective for potential cancer treatment based on tumor-specific cuproptosis by controlling the degradation behaviors of Cu-based nanomaterials.

Source: Chemical Engineering Journal

DOI: 10.1016/j.cej.2024.156753

Authors: Panfeng Wang, Lijun Ren, Yifan Tang, Bo Yuan, Bijiang Geng, Yin Zhao