Selective inhibition of partial EMT-induced tumour cell growth by cerium valence states of extracellular ceria nanoparticles for anticancer treatment

Tamaki Naganuma

doi:10.1016/j.colsurfb.2024.113794

Article Selective inhibition of partial EMT-induced tumour cell growth by cerium valence states of extracellular ceria nanoparticles for anticancer treatment

Tamaki Naganuma (National Institute for Materials Science)

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Tamaki Naganuma. Selective inhibition of partial EMT-induced tumour cell growth by cerium valence states of extracellular ceria nanoparticles for anticancer treatment. Colloids and Surfaces B: Biointerfaces. 2024, 236 (), 113794. https://doi.org/10.1016/j.colsurfb.2024.113794

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Targeting specific tumour cells and their microenvironments is essential for enhancing the efficacy of chemotherapy and reducing its side effects. A partial epithelial-to-mesenchymal transition state (pEMT, with a hybrid epithelial/mesenchymal phenotype) in tumour cells is an attractive targeting for anticancer treatment because it potentially provides maximal stemness and metastasis relevant to malignant cancer stem cell-like features. However, treatment strategies to target pEMT in tumour cells remain a challenge. This study demonstrates that extracellular cerium oxide nanoparticles (CNPs) selectively inhibit the growth of pEMT-induced tumour cells, without affecting full epithelial tumour cells. Herein, highly concentrated Ce³⁺ and Ce⁴⁺ ions are formed on CNPlayered poly-L-lactic acid surfaces. Cell cultures of pEMT-induced and uninduced lung cancer cell lines on the CNP-layered substrates allow the effect of extracellular CNPs on tumour cell growth to be investigated. The extracellular CNPs with dominant Ce³⁺ and Ce⁴⁺ ions were able to trap pEMT-induced tumour cells in a growtharrested quiescent/dormant or cytostatic state without generating redox-related reactive oxygen species (ROS), i.e. non-redox mechanisms. The dominant Ce³⁺ state provided highly efficient growth inhibition of the pEMTinduced tumour cells. In contrast, the dominant Ce⁴⁺ state showed highly selective and appropriate growth regulation of normal and tumour cells, including a mesenchymal phenotype. Furthermore, Ce⁴⁺-CNPs readily adsorbed serum-derived fibronectin and laminin. Cerium valence-specific proteins adsorbed on CNPs may influence receptor-mediated cell-CNP interactions, leading to tumour cell growth inhibition. These findings provide new perspectives for pEMT-targeting anticancer treatments based on the unique biointerface of extracellular CNPs with different Ce valence states.

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