Design of Cationic Multiwalled Carbon Nanotubes as Efficient siRNA Vectors for Lung Cancer Xenograft Eradication

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• 作者：Chang Guo ; Wafa T. Al-Jamal ; Francesca M. Toma ; Alberto Bianco ; Maurizio Prato ; Khuloud T. Al-Jamal ; Kostas Kostarelos
• 刊名：Bioconjugate Chemistry
• 出版年：2015
• 出版时间：July 15, 2015
• 年：2015
• 卷：26
• 期：7
• 页码：1370-1379
• 全文大小：479K
• ISSN：1520-4812

文摘

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.