IF 10.2! Efficient On-Demand Induction of Copper Proliferation in Triple-Negative Breast Cancer via Dual-Reaction Black Phosphorus Nanosheets

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Cuproptosis is a newly discovered cell death pathway. Our analysis indicates that this pathway is closely associated with the clinical prognosis of patients with triple-negative breast cancer and may potentially facilitate the elimination of triple-negative breast cancer. However, precisely and efficiently regulating cuproptosis within tumor regions in a controllable manner remains challenging. In this study, we developed a highly effective cuproptosis inducer based on black phosphorus nanosheets (BPNs@Cu@PDA, abbreviated as BCP).It has copper ion release characteristics that respond to both acid and heat, and it also enhances the loading capacity of cuprous ions. In short, BCP effectively increases the proportion of loaded cuprous ions through the intrinsic surface redox reaction between phosphorus and copper ions, thereby significantly enhancing copper-mediated cytotoxicity. After accumulating in tumor regions, BCP can respond to the photothermal effect created by dopamine modification and the acidic microenvironment, precisely releasing cuprous/copper ions, which in turn efficiently generate reactive hydroxyl radicals through copper ion-dependent Fenton-like reactions.This leads to significant oxidative damage in triple-negative breast cancer cells. The precisely released sub-copper/copper ions further inhibit the formation of iron-sulfur clusters, while also causing the aggregation of succinylated proteins, resulting in severe disruption of mitochondrial function and the tricarboxylic acid cycle. This synergistically induces pronounced cuproptosis and subsequent suppression of triple-negative breast cancer (with tumor volume reduced by over 90%). This study proposes a novel cuproptosis-inducing strategy for triple-negative breast cancer with negligible toxicity, which may provide new insights for the clinical treatment of triple-negative breast cancer.

Original link

Efficient on-demand cuproptosis induction against triple-negative breast cancer via dual-responsive black phosphorus nanosheet

Pub Date : 2025-06-13

DOI: 10.1016/j.mtbio.2025.101985

Qiancun Hong,  Jiajun Huang,  Zhiguo Li,  Yue Chen,  Jiawei Wang,  Tongrui Shang,  Zelin Chen,  Cong Luo,  Yongqiang Wang,  Xinghong Tang,  Taojian Fan,  Songyin Huang,  Hao Fu,  Yandan Yao