Design of Cationic Multi-Walled Carbon Nanotubes as Efficient siRNA Vectors for Lung Cancer Xenograft Eradication

Chang Guo, Wafa T Al-Jamal, Francesca M Toma, Alberto Bianco, Maurizio Prato, Khuloud T Al-Jamal, Kostas Kostarelos

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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 intratumoural 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 RT-PCR and Western blot, in addition to TUNEL staining confirmed the biological functionality of the siRNA intratumourally, suggesting that tumor eradication was due to PLK1 knockdown. Furthermore, by using a fluorescently labelled, non-coding 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.
Original languageEnglish
Pages (from-to)1370–1379
JournalBioconjugate Chemistry
Volume26
Issue number7
Early online date3 Jun 2015
DOIs
Publication statusPublished - 2015

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