title: Therapeutic targeting of polo-like kinase 1 using RNA-interfering nanoparticles (iNOPs) for the treatment of non-small cell lung cancer.
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.
authors.affiliation: Children's Cancer Institute, Lowy Cancer Research Centre, Randwick, UNSW Australia (UNSW), NSW, Australia.|ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Australian Centre for NanoMedicine, UNSW, NSW, Australia.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: McCarroll
authors.affiliation: Children's Cancer Institute, Lowy Cancer Research Centre, Randwick, UNSW Australia (UNSW), NSW, Australia.
authors.forename: Tanya
authors.initials: T
authors.lastname: Dwarte
authors.affiliation: Program for RNA Biology, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA.
authors.forename: Huricha
authors.initials: H
authors.lastname: Baigude
authors.affiliation: Program for RNA Biology, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA.|Department of Pediatrics, University of California, San Diego, School of Medicine, La Jolla, CA, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Dang
authors.affiliation: Children's Cancer Institute, Lowy Cancer Research Centre, Randwick, UNSW Australia (UNSW), NSW, Australia.
authors.forename: Lu
authors.initials: L
authors.lastname: Yang
authors.affiliation: Children's Cancer Institute, Lowy Cancer Research Centre, Randwick, UNSW Australia (UNSW), NSW, Australia.|ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Australian Centre for NanoMedicine, UNSW, NSW, Australia.
authors.forename: Rafael B
authors.initials: RB
authors.lastname: Erlich
authors.affiliation: Children's Cancer Institute, Lowy Cancer Research Centre, Randwick, UNSW Australia (UNSW), NSW, Australia.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Kimpton
authors.affiliation: Children's Cancer Institute, Lowy Cancer Research Centre, Randwick, UNSW Australia (UNSW), NSW, Australia.|ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Australian Centre for NanoMedicine, UNSW, NSW, Australia.
authors.forename: Joann
authors.initials: J
authors.lastname: Teo
authors.affiliation: Children's Cancer Institute, Lowy Cancer Research Centre, Randwick, UNSW Australia (UNSW), NSW, Australia.|ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Australian Centre for NanoMedicine, UNSW, NSW, Australia.
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Sagnella
authors.affiliation: Children's Cancer Institute, Lowy Cancer Research Centre, Randwick, UNSW Australia (UNSW), NSW, Australia.
authors.forename: Mia C
authors.initials: MC
authors.lastname: Akerfeldt
authors.affiliation: Pancreatic Cancer Translational Research Group, Lowy Cancer Research Centre, Prince of Wales Clinical School, UNSW, NSW, Australia.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Australian Centre for NanoMedicine, UNSW, NSW, Australia.|Pancreatic Cancer Translational Research Group, Lowy Cancer Research Centre, Prince of Wales Clinical School, UNSW, NSW, Australia.
authors.forename: Phoebe A
authors.initials: PA
authors.lastname: Phillips
authors.affiliation: Program for RNA Biology, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA.|Department of Pediatrics, University of California, San Diego, School of Medicine, La Jolla, CA, USA.
authors.forename: Tariq M
authors.initials: TM
authors.lastname: Rana
authors.affiliation: Children's Cancer Institute, Lowy Cancer Research Centre, Randwick, UNSW Australia (UNSW), NSW, Australia.|ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Australian Centre for NanoMedicine, UNSW, NSW, Australia.
authors.forename: Maria
authors.initials: M
authors.lastname: Kavallaris
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000628:therapy*; D018797:Cell Cycle Proteins / Q000235:genetics*; D049109:Cell Proliferation; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000628:therapy*; D051379:Mice; D053758:Nanoparticles; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D034622:RNA Interference / Q000276:immunology*; D034741:RNA, Small Interfering / Q000235:genetics*; D014162:Transfection; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D000097869:Polo-Like Kinase 1
keywords: Polo-like kinase 1; interfering nanoparticles; non-small cell lung cancer; orthotopic non-small cell lung cancer mouse model; siRNA