Design of Cationic Multiwalled Carbon Nanotubes as Efficient siRNA Vectors for Lung Cancer Xenograft Eradication.
Fiche publication
Date publication
juillet 2015
Journal
Bioconjugate chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BIANCO Alberto
Tous les auteurs :
Guo C, Al-Jamal WT, Toma FM, Bianco A, Prato M, Al-Jamal KT, Kostarelos K
Lien Pubmed
Résumé
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.
Mots clés
Animals, Apoptosis, Cations, chemistry, Cell Cycle Proteins, genetics, Cell Line, Tumor, Female, Genetic Vectors, administration & dosage, Humans, Lung, metabolism, Lung Neoplasms, genetics, Mice, Nude, Nanotubes, Carbon, chemistry, Protein-Serine-Threonine Kinases, genetics, Proto-Oncogene Proteins, genetics, RNA Interference, RNA, Small Interfering, administration & dosage, RNAi Therapeutics
Référence
Bioconjug Chem. 2015 Jul 15;26(7):1370-9