A heterojunction-engineering nanodrug with tumor microenvironment responsiveness for tumor-specific cuproptosis and chemotherapy amplified sono-immunotherapy

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials Pub Date : 2025-04-02 DOI:10.1016/j.biomaterials.2025.123319

Yang Wang , Tingting Yan , Jinming Cai , Hongjing Dou , Yu Zhu , Bijiang Geng , Dengyu Pan , Longxiang Shen

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引用次数: 0

Abstract

Cuproptosis has recently identified as a unique copper-dependent cell death mechanism that may provide new opportunities for improving the therapeutic effect of tumor therapy through triggering efficient adaptive immune responses. However, the poor delivery efficiency and non-tumor-specific release of Cu ions would restrict the potential clinical applications of cuproptosis inducers. Herein, we report for the first time the development of hollow Cu_2-xSe nanocubes as the tumor microenvironment (TME)-responsive drug delivery systems and cuproptosis inducers for tumor-specific chemotherapy and cuproptosis. The presence of Cu vacancy endows Cu_2-xSe with excellent sonodynamic and chemodynamic activity. The hollow Cu_2-xSe nanocubes with TME-responsive degradation behaviors are further utilized to load graphene quantum dot (GQD) nanodrugs to form GQD/Cu_2-xSe heterojunctions for achieving tumor-specific chemotherapy. The heterojunction-fabrication GQD/Cu_2-xSe exhibits amplified ROS generation capabilities and improved TME regulation ability owing to the optimized electron-hole separation kinetics. More importantly, the significant increase in ROS levels and efficient cuproptosis could reverse the immunosuppressive TME and induce immunogenic cell death that stimulates strong systemic immune responses to eliminate tumors. Collectively, this work presents an innovative strategy for the utilization of TME-responsive cuproptosis inducers for tumor-specific chemotherapy and cuproptosis augmented sono-immunotherapy.

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来源期刊

Biomaterials 工程技术-材料科学：生物材料

CiteScore

26.00

自引率

2.90%

发文量

565

审稿时长

46 days

期刊介绍： Biomaterials is an international journal covering the science and clinical application of biomaterials. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. It is the aim of the journal to provide a peer-reviewed forum for the publication of original papers and authoritative review and opinion papers dealing with the most important issues facing the use of biomaterials in clinical practice. The scope of the journal covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. These sciences include polymer synthesis and characterization, drug and gene vector design, the biology of the host response, immunology and toxicology and self assembly at the nanoscale. Clinical applications include the therapies of medical technology and regenerative medicine in all clinical disciplines, and diagnostic systems that reply on innovative contrast and sensing agents. The journal is relevant to areas such as cancer diagnosis and therapy, implantable devices, drug delivery systems, gene vectors, bionanotechnology and tissue engineering.