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Oncotarget. 2015 May 20;6(14):12020-34.

Therapeutic targeting of polo-like kinase 1 using RNA-interfering nanoparticles (iNOPs) for the treatment of non-small cell lung cancer.

Author information

1
Children's Cancer Institute, Lowy Cancer Research Centre, Randwick, UNSW Australia (UNSW), NSW, Australia.
2
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Australian Centre for NanoMedicine, UNSW, NSW, Australia.
3
Program for RNA Biology, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA.
4
Department of Pediatrics, University of California, San Diego, School of Medicine, La Jolla, CA, USA.
5
Pancreatic Cancer Translational Research Group, Lowy Cancer Research Centre, Prince of Wales Clinical School, UNSW, NSW, Australia.

Abstract

Non-small cell lung cancer (NSCLC) remains the most common cause of cancer death worldwide due its resistance to chemotherapy and aggressive tumor growth. Polo-like kinase 1 (PLK1) is a serine-threonine protein kinase which is overexpressed in cancer cells, and plays a major role in regulating tumor growth. A number of PLK1 inhibitors are in clinical trial; however, poor tumor bioavailability and off-target effects limit their efficacy. Short-interfering-RNA (siRNA) holds promise as a class of therapeutics, which can selectively silence disease-causing genes. However, siRNA cannot enter cells without a delivery vehicle. Herein, we investigated whether RNAi-interfering nanoparticles could deliver siRNA to NSCLC cells and silence PLK1 expression in vitro and in vivo. iNOP-7 was non-toxic, and delivered siRNA with high efficiency to NSCLC cells. iNOP-7-PLK1 siRNA silenced PLK1 expression and reduced NSCLC growth in vitro. Notably, iNOP-7 delivered siRNA to orthotopic lung tumors in mice, and administration of iNOP-7-PLK1 siRNA reduced lung tumor burden. These novel data show that iNOP-7 can deliver siRNA against PLK1 to NSCLC cells, and decrease cell proliferation both in vitro and in vivo. iNOP-7-PLK1 siRNA may provide a novel therapeutic strategy for the treatment of NSCLC as well as other cancers which aberrantly express this gene.

KEYWORDS:

Polo-like kinase 1; interfering nanoparticles; non-small cell lung cancer; orthotopic non-small cell lung cancer mouse model; siRNA

PMID:
25557168
PMCID:
PMC4494920
DOI:
10.18632/oncotarget.2664
[Indexed for MEDLINE]
Free PMC Article

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