Ultra-small platinum nanoparticles on gold nanorods induced intracellular ROS fluctuation to drive megakaryocytic differentiation of leukemia cells.

Tao Wen, Aiyun Yang, Tao Wang, Mengfan Jia, Xinning Lai, Jie Meng, Jian Liu, Bing Han, Haiyan Xu

Biomaterials science 2020 Nov 10

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Chronic myeloid leukemia (CML) is a kind of hematological malignancy featured with retarded differentiation that is highly linked to the level of intracellular reactive oxygen species (ROS). In this work, ultra-small platinum nanoparticles deposited on gold nanorods (Au@Pt) were synthesized and applied on the CML cells. It was shown that Au@Pt had multienzyme-like activities that induced a fluctuation of the intracellular ROS level over the incubation time, depending on their temporal locations in the cells. The ROS fluctuation triggered cellular autophagy and enhanced the level of autophagic protein Beclin-1, which caused the degradation of fusion protein BCR-ABL, the key factor of retarded differentiation and led to the downregulation of phosphorylation of PI3K and AKT. These interactions together broke retarded differentiation and drove the CML cells to differentiate towards megakaryocytes, which is of great significance in enhancing leukemic cell apoptosis. Therefore, Au@Pt exhibited a novel function and promising therapeutic potential for the CML treatment.

Citation

Tao Wen, Aiyun Yang, Tao Wang, Mengfan Jia, Xinning Lai, Jie Meng, Jian Liu, Bing Han, Haiyan Xu. Ultra-small platinum nanoparticles on gold nanorods induced intracellular ROS fluctuation to drive megakaryocytic differentiation of leukemia cells. Biomaterials science. 2020 Nov 10;8(22):6204-6211