Nature Communications
Nature Communications
4 years ago

Lipoprotein-biomimetic nanostructure enables efficient targeting delivery of siRNA to Ras-activated glioblastoma cells via macropinocytosis

Lipoprotein-biomimetic nanostructure enables efficient targeting delivery of siRNA to Ras-activated glioblastoma cells via macropinocytosis
, Yong-Ming Qiu, Xiao-Ling Gao, Gan Jiang, Jia-Lin Huang, Xiao Gu, Xiao-Lin Wang, Xin-Guo Jiang, Meng Hu, Ying-Ying Lin, Jun-Feng Feng, Le-Pei Chen, Qing-Xiang Song, Jun Chen, , Di Jiang, Hong-Zhuan Chen, Hua-Hua Song, Ji-Yao Jiang,
Hyperactivated Ras regulates many oncogenic pathways in several malignant human cancers including glioblastoma and it is an attractive target for cancer therapies. Ras activation in cancer cells drives protein internalization via macropinocytosis as a key nutrient-gaining process. By utilizing this unique endocytosis pathway, here we create a biologically inspired nanostructure that can induce cancer cells to ‘drink drugs’ for targeting activating transcription factor-5 (ATF5), an overexpressed anti-apoptotic transcription factor in glioblastoma. Apolipoprotein E3-reconstituted high-density lipoprotein is used to encapsulate the siRNA-loaded calcium phosphate core and facilitate it to penetrate the blood–brain barrier, thus targeting the glioblastoma cells in a macropinocytosis-dependent manner. The nanostructure carrying ATF5 siRNA exerts remarkable RNA-interfering efficiency, increases glioblastoma cell apoptosis and inhibits tumour cell growth both in vitro and in xenograft tumour models. This strategy of targeting the macropinocytosis caused by Ras activation provides a nanoparticle-based approach for precision therapy in glioblastoma and other Ras-activated cancers.

Publisher URL: http://www.nature.com/articles/ncomms15144

DOI: 10.1038/ncomms15144

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