Nanoparticle-Delivered siRNA Shrinks Tumors in Mouse Model

Cancer researchers employed a nanoparticle delivery system to deliver short interfering RNA (siRNA) that blocked the activity of Twist-related protein 1 (TWIST1), which prevented growth and spread of tumors in a mouse model.

TWIST1, also known as class A basic helix-loop-helix protein 38 (bHLHa38), is a basic helix-loop-helix transcription factor that in humans is encoded by the TWIST1 gene. TWIST1 is a transcription factor whose reactivation in tumors leads to epithelial to mesenchymal transition (EMT), including increased cancer stem cell-like behavior, survival, and invasiveness.

Investigators at the University of California, Los Angeles (USA) used polyethyleneimine-coated mesoporous silica nanoparticles (containing pores with diameters between 2 and 50 nanometers)) to deliver TWIST1 siRNA to mice bearing xenograft tumors. The mice were treated with intravenous injections of the siRNA-nanoparticles weekly for six weeks.

Results published in the June 23, 2015, online edition of the journal Nanomedicine: Nanotechnology, Biology and Medicine revealed that weekly siRNA treatment slowed tumor growth and inhibited not only TWIST1 but also other genes under the control of the epithelial-mesenchymal transition process.

“We were truly surprised by the dramatic effect of delivering TWIST1 siRNA,” said contributing author Dr. Fuyu Tamanoi, professor of microbiology, immunology, and molecular genetics at the University of California, Los Angeles. “This demonstrates the effectiveness of our treatment and encourages us to explore further what is happening to the tumor.”

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