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

AIMS [Gd@C(82)(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@C(82)(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@C(82)(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@C(82)(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@C(82)(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@C(82)(OH)(22)](n).

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