title: Design of Cationic Multiwalled Carbon Nanotubes as Efficient siRNA Vectors for Lung Cancer Xenograft Eradication.
abstract: Polo-Like Kinase (PLK1) has been identified as a potential target in cancer gene therapy via chemical or genetic inhibitory approaches. The biomedical applications of chemically functionalized carbon nanotubes (f-CNTs) in cancer therapy have been studied due to their ability to efficiently deliver siRNA intracellularly. In this study, we established the capacity of cationic MWNT-NH3(+) to deliver the apoptotic siRNA against PLK1 (siPLK1) in Calu6 tumor xenografts by direct intratumoral injections. A direct comparison with cationic liposomes was made. This study validates the PLK1 gene as a potential target in cancer gene therapy including lung cancer, as demonstrated by the therapeutic efficacy of siPLK1:MWNT-NH3(+) complexes and their ability to significantly improve animal survival. Biological analysis of the siPLK1:MWNT-NH3(+) treated tumors by qRT-PCR and Western blot, in addition to TUNEL staining confirmed the biological functionality of the siRNA intratumorally, suggesting that tumor eradication was due to PLK1 knockdown. Furthermore, by using a fluorescently labeled, noncoding siRNA sequence complexed with MWNT-NH3(+), we established for the first time that the improved therapeutic efficacy observed in f-CNT-based siRNA delivery is directly proportional to the enhanced siRNA retention in the solid tumor and subsequent uptake by tumor cells after local administration in vivo.
authors.affiliation: †Nanomedicine Lab, UCL School of Pharmacy, Faculty of Life Sciences, University College London, London WC1N 1AX, United Kingdom.
authors.forename: Chang
authors.initials: C
authors.lastname: Guo
authors.affiliation: †Nanomedicine Lab, UCL School of Pharmacy, Faculty of Life Sciences, University College London, London WC1N 1AX, United Kingdom.
authors.forename: Wafa T
authors.initials: WT
authors.lastname: Al-Jamal
authors.affiliation: ‡Center of Excellence for Nanostructured Materials, Department of Chemical and Pharmaceutical Sciences, University of Trieste, 34127 Trieste, Italy.
authors.forename: Francesca M
authors.initials: FM
authors.lastname: Toma
authors.affiliation: §CNRS, Institut de Biologie Moléculaire et Cellulaire, UPR 3572, Immunopathologie et Chimie Thérapeutique, 67000 Strasbourg, France.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bianco
authors.affiliation: ‡Center of Excellence for Nanostructured Materials, Department of Chemical and Pharmaceutical Sciences, University of Trieste, 34127 Trieste, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Prato
authors.affiliation: †Nanomedicine Lab, UCL School of Pharmacy, Faculty of Life Sciences, University College London, London WC1N 1AX, United Kingdom.
authors.forename: Khuloud T
authors.initials: KT
authors.lastname: Al-Jamal
authors.affiliation: †Nanomedicine Lab, UCL School of Pharmacy, Faculty of Life Sciences, University College London, London WC1N 1AX, United Kingdom.
authors.forename: Kostas
authors.initials: K
authors.lastname: Kostarelos
mesh_terms: D000818:Animals; D017209:Apoptosis; D002412:Cations / Q000737:chemistry; D018797:Cell Cycle Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D008819:Mice, Nude; D037742:Nanotubes, Carbon / Q000737:chemistry*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D000067492:RNAi Therapeutics; D000097869:Polo-Like Kinase 1
chemical_list: D002412:Cations; D018797:Cell Cycle Proteins; D037742:Nanotubes, Carbon; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D000097869:Polo-Like Kinase 1