A triboelectric-field-mediated cuproptosis induction patch for melanoma recurrence suppression

Cutaneous melanoma, a prevalent and highly aggressive malignancy with poor prognosis, frequently leads to postoperative recurrence, presenting a significant therapeutic challenge. One of the promising cancer therapeutic methods is the induction of cuproptosis, a copper-triggered modality of mitochondrial cell death. However, its therapeutic efficacy is often limited by insufficient copper uptake and intracellular accumulation. Herein, we present a flexible and self-powered electronic patch by integrating an ultra-thin triboelectric nanogenerator (TENG) with copper-loaded nitrogen-doped carbon nanoparticles (Cu(II)-NC NPs). Extensive experimental and molecular dynamics simulation results demonstrate that the triboelectric field efficiently modulates plasma membrane permeability and fluidity, facilitating the uptake of Cu(II)-NC NPs into melanoma cells. The resulting intracellular copper accumulation increases the production of hydroxyl radicals and the depletion of glutathione, synergizing with cuproptosis to amplify copper-induced cell death. In a mouse model with incomplete melanoma resection, the patch effectively inhibits melanoma recurrence, offering a novel therapeutic paradigm to promote cancer therapy.