Fucoidan-Copper Nanoparticles to Potentiate Synergistic Cancer Cell Cuproptosis and Immunotherapy

Chen, H.; Pang, X.-H.; Wang, Q.-H.; Chen, Z.; Zhuang, L.-l.; Luo, J.-y.; Zheng, Q.-x.; Zhong, R.-f.; Zhan, X.-m.; Yang, L.; Zhu, L.; Jiang, J.-G.

doi:10.1101/2024.10.20.619277

bioRxiv · 10.1101/2024.10.20.619277

Fucoidan-Copper Nanoparticles to Potentiate Synergistic Cancer Cell Cuproptosis and Immunotherapy

Chen, H.·Pang, X.-H.·Wang, Q.-H.·Chen, Z.·Zhuang, L.-l.·Luo, J.-y.·Zheng, Q.-x.·Zhong, R.-f.·Zhan, X.-m.·Yang, L.·Zhu, L.·Jiang, J.-G.

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Abstract

Cuproptosis, a newly characterized form of regulated cell death initiated by copper binding to lipoylated components of the tricarboxylic acid cycle, presents a promising target for cancer therapy. Here, we report the development of fucoidan-copper nanoparticles (Fu-Cu) that exploit this mechanism to selectively induce cytotoxicity in HuH-7 liver cancer cells. The Fu-Cu was synthesized using fucoidan, a sulfated polysaccharide with inherent anticancer properties, as a natural nanocarrier for copper ions. Characterization confirmed successful copper incorporation and the formation of stable nanoparticles. Fu-Cu treatment enhanced intracellular copper levels and oxidative stress, triggering cuproptosis mediated by mitochondrial carrier homolog 2. Knockout of ferredoxin 1 in HuH-7 cells mitigated the cytotoxic effects, underscoring its critical role in copper-induced cell death. In vivo studies using a subcutaneous tumor model in BALB/c nude mice demonstrated that Fu-Cu effectively inhibited tumor growth and stimulated antitumor immunity, evidenced by increased infiltration of T cells, natural killer cells, and macrophages within the tumor microenvironment. These findings highlight Fu-Cu as a novel therapeutic strategy for HCC, leveraging the mechanism of cuproptosis and immune activation to suppress tumor progression.

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Chen, H., Pang, X.-H., Wang, Q.-H., Chen, Z., Zhuang, L.-l., Luo, J.-y., Zheng, Q.-x., Zhong, R.-f., Zhan, X.-m., Yang, L., Zhu, L., Jiang, J.-G.. 2024-10-23. Fucoidan-Copper Nanoparticles to Potentiate Synergistic Cancer Cell Cuproptosis and Immunotherapy. https://doi.org/10.1101/2024.10.20.619277

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