Engineered Cu-VT composite nanoparticles induce copper-dependent cell death in bladder cancer: insights from single-cell spatial transcriptomics

Abstract

Bladder cancer (BLCA), particularly due to the high recurrence and progression rates of non-muscle-invasive bladder cancer (NMIBC), is a significant global health challenge. Current treatments, such as Bacillus Calmette-Guérin (BCG) immunotherapy and intravesical chemotherapy, often cause substantial side effects and exhibit limited efficacy, highlighting the urgent need for novel therapeutic strategies. Single-cell spatial transcriptomic advancements have identified cuproptosis as a critical pathway in BLCA, presenting a promising target for treatment. In this study, these insights were leveraged to design Cu-VT nanoparticles (NPs), an innovative composite material that combines the unique properties of copper ions and the natural flavonoid vitexin, to induce cuproptosis. Cu-VT NPs could effectively induce apoptosis and oxidative stress in BLCA cells concurrently modulating the immune response within the tumor microenvironment. Comprehensive in vitro and in vivo experiments demonstrated that Cu-VT NPs significantly inhibited tumor growth and reduced lung metastasis through cuproptosis induction. This dual-function composite material enhances therapeutic efficacy and minimizes side effects, showcasing its potential as a revolutionary treatment for BLCA. Our findings highlight the transformative potential of Cu-VT NPs in the context of BLCA treatment, establishing a new paradigm in the use of composite materials for the treatment of advanced cancer.