Multifunctional Cu2-xSe nanomaterials for cancer theranostics: recent advances, therapeutic mechanisms, and translational challenges

Cu2-xSe has made many breakthroughs in tumor therapy due to its unique advantages. Cu2-xSe can enhance immunotherapy by multiple mechanisms, such as reshaping the immunosuppressive tumor microenvironment (TME) and triggering immunogenic cell death. Cu2-xSe possesses a variety of nanozyme-like activities that can disrupt the redox homeostasis of tumor cells and modulate the TME, enabling chemodynamic therapy (CDT) and improving the efficacy of multiple therapeutic modalities. Cu2-xSe not only acts as a cuproptosis inducer and an autophagy inhibitor, but also induces cell-cycle arrest and impairs mitochondrial function, thereby suppressing tumor proliferation and metastasis. Cu2-xSe is a multifunctional nanotheranostic agent that not only possesses photoacoustic imaging (PAI) property, but also exhibits excellent thermoelectric catalytic therapy (TECT), photothermal therapy (PTT) and photodynamic therapy (PDT) functions, making it suitable for combined therapy and imaging-guided therapy. At present, studies on Cu2-xSe-based tumor therapy have reported a series of encouraging findings that warrant systematic summary and analysis to promote the development of nanomedicine. So far, there is no review article on the applications of Cu2-xSe in tumor diagnosis and therapy. In this review, we summarize the recent progress and prospects of Cu2-xSe in cancer diagnosis and therapy, focusing on the breakthroughs of Cu2-xSe in new strategies for tumor diagnosis and treatment and in solving medical problems. This review intends to offer insights that may accelerate the development of Cu2-xSe-based nanomedicine for cancer therapy.