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Novel Ce/Cu-modified black ceramics disrupted mitochondrial dysfunction and tricarboxylic acid cycle to induce cuproptosis in osteosarcoma cells.

Rongxiang Zhang,Xuelei Yin,Zenghui Xu,Qikang Yan

Published 2025 in Biomaterials Advances

ABSTRACT

PURPOSE Development of Ce/Cu-modified black ceramics and investigation of the mechanism of anti-osteosarcoma activity. METHODS Black ceramics doped with 0.3-0.7 wt% CeO2 and CuO were prepared and analyzed using energy-dispersive X-ray spectroscopy (EDS), compression stress-strain tests, weight change, and antibacterial assays. MNNG/HOS and MG63 cells were seeded on ceramic substrates, and their adhesion and morphology were analyzed using scanning electron microscopy (SEM) and phalloidin staining. In vitro, we first assessed the anti-tumor effects of ceramic materials, then validated their impact on cuproptosis by measuring Cu2+ levels and the expression of related proteins, including SLC31A1, HSP70, and ATP7A. Mitochondrial dysfunction and TCA abnormalities were assessed by measuring mitochondrial membrane potential, reactive oxygen species, mitochondrial structure, TCA cycle metabolites (citric acid and lactic acid), ATP levels, and DLAT and LIAS protein levels. The cuproptosis inhibitor TTM, PI3K activator 740YP, and AKT activator SC79 were used to explore the relationship between cuproptosis and the PI3K/AKT pathway in osteosarcoma cells treated with Ce/Cu-doped black ceramics. RESULTS Our research confirmed the superior anti-tumor properties of the Ce/Cu-modified black ceramic and its potential mechanisms against osteosarcoma. The Ce/Cu-doped black ceramic caused mitochondrial dysfunction and disrupted TCA cycle metabolism, resulting in cuproptosis in MNNG/HOS and MG63 cells. The PI3K/AKT pathway was involved in cuproptosis in osteosarcoma cells treated with Ce/Cu-modified ceramics. CONCLUSION Our research confirmed that Ce/Cu-modified black ceramics have superior anti-tumor effects and potential mechanisms, confirming the clinical potential of Ce/Cu-modified black ceramics in cancer treatment and providing theoretical basis for the clinical translation.

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