Nanotech 2011

Design of Cationic Multi-Walled Carbon Nanotubes as Efficient siRNA Vectors for Tumour Eradication in Vivo

K.T. Al-Jamal, C. Guo, W.T. Al-Jamal, M.A. Herrero, F.M. Toma, A. Bianco, M. Prato, K. Kostarelos
King’s College London, UK

Keywords: RNAi, cancer, carbon nanotubes, lung, nanomedicine

Abstract:

RNA interference (RNAi) is being studied extensively for its application in cancer therapy. Oncogenes as well as genes involved in angiogenesis, apoptosis, metastasis and chemotherapy resistance have all been proposed as promising targets. Complexes between siRNA and cationic liposomes and polymers have been described and are currently developed for the treatment of a variety of cancer preclinical models. Carbon nanotubes (CNT) have been recently proposed as novel nanomaterials that can offer significant advantages for the intracellular delivery of nucleic acids, such as siRNA. We have recently demonstrated in a proof-of-principle study (1) that amino-functionalized multi-walled carbon nanotubes (MWNT-NH3+) can effectively deliver in vivo a proprietary siRNA sequence (siTOX®) triggering cell apoptosis that results in human lung xenograft (Calu6) eradication and prolonged survival. Herein, we have investigated the use of the same functionalized carbon nanotubes material, to design a vector for non-viral delivery of small interference RNA (siRNA) directly into the tumor to knock down the Polo-like kinase 1 (PLK1) gene. This was based on the hypothesis that siRNA against PLK1could lead to tumour apoptosis and improved survival of the tumour-bearing mice. The direct comparison between carbon nanotubes and cationic liposomes demonstrates the potential advantages offered by carbon nanotubes for the intracellular delivery of therapeutic agents in vivo. Whole animal fluorescence imaging showed improved retention of the fluorescently labeled siRNA into Calu6 xenografts when complexed to MWNT-NH3+ in comparison to cationic liposomes. Western blot and RT-PCR analysis have confirmed more significant PLK1 gene knockdown in MWNT-NH3+:siPLK1 treated group.
 

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