Metallofullerol nanoparticles with low toxicity inhibit tumor growth by induction of G0/G1 arrest

Aims: [Gd@C₈₂(OH)₂₂]_n is a new type of nanoparticle with potent antineoplastic activity and low toxicity compared with traditional drugs. In this study, we explored, for the first time, the effect of [Gd@C₈₂(OH)₂₂]_n on the cell cycle using human breast cancer MCF-7 and human umbilical vein endothelial ECV304 cell lines by flow cytometry. Methods: Cell viability was assessed through CCK-8 assay, and MCF-7 tumor-bearing mice were examined after 2 weeks of treatment with [Gd@C₈₂(OH)₂₂]_n. Cell cycle-related gene expression was detected by microarray and confirmed by real-time PCR and RNAi. Results: Cell viability studies confirmed that [Gd@C₈₂(OH) ₂₂]_n inhibits breast cancer effectively with very low toxicity. Flow cytometric data and microarray results reveal that [Gd@C ₈₂(OH)₂₂]_n mediates G0/G1 arrest in both cell lines by regulating the expression of several genes, such as cyclin D2, cyclin E and CDK4, among others, in the related cell cycle. Conclusion: Results further demonstrated that [Gd@C₈₂(OH)₂₂]_n could inhibit tumor growth by inducing tumor cell and vein endothelial cell G0/G1 arrest, which may explain the low toxicity of [Gd@C₈₂(OH)₂₂] _n.