Blocking stemness and metastatic properties of ovarian cancer cells by targeting p70S6K with dendrimer nanovector-based siRNA delivery
Jing Ma, Shashwati Kala, Susan Yung, Tak Mao Chan, Yu Cao, Yifan Jiang, Xiaoxuan Liu, Suzanne Giorgio, Ling Peng, and Alice ST Wong
Mol. Ther., 2018, 26, 70-83
Metastasis is the cause of most (>90%) cancer deaths, and currently lack of effective treatments. In this study, we demonstrate the potential advantages of using rationally designed siRNA that targets cancer stem cells (CSCs) in combination with dendrimer nanotechnology-based siRNA delivery for efficacious treatment of metastasis using ovarian cancer as the cancer model. The structurally flexible poly(amidoamine) dendrimer of generation 6 (G6) formed stable and uniform nanoparticles with p70S6k siRNA, which protected the siRNA from degradation and significantly decreased the kinase p70S6K at both mRNA and protein levels in ovarian CSCs, leading to a marked reduction in CSC proliferation and expansion without obvious toxicity towards normal cells. In addition, treatment with the siRNA/dendrimer nanoparticles substantially decreased mesothelial interaction, migration and invasion of CSCs in vitro as well as tumor growth and metastasis in CSC xenograft mice in vivo. Altogether, these results highlight that the use of siRNA in combination with dendrimer nanotechnology-based delivery constitute a new approach for molecularly targeted cancer therapy to treat metastasis.
This work is issued from collaboration between Dr. Ling Peng at the CNRS/Aix-Marseille University in France and Prof. Alice ST Wong at the University of Hong Kong in China.
Contact : Ling Peng
Ref : Ma et al, Mol. Ther., 2018, 26, 70-83. (DOI : 10.1016/j.ymthe.2017.11.006