NSTI BioNano 2010

Enhanced cellular internalisation and gene silencing with a series of cationic dendron-multiwalled carbon nanotube:siRNA complexes

K.T. Al-Jamal, F.M. Toma, A. Yilmazer, H. Ali-Boucetta, A. Nunes, M.A. Herrero, B. Tian, A. Bianco, M. Prato, K. Kostarelos
The School of Pharmacy, UK

Keywords: siRNA, dendron, carbon nanotubes, cellular uptake, delivery

Abstract:

One of the major obstacles to the clinical development of gene silencing by small interfering RNA (siRNA) is its effective cytoplasmic delivery. Carbon nanotubes 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 (f-MWNT) can effectively deliver in vivo an siRNA sequence triggering cell apoptosis that results in human lung xenograft eradication and prolonged survival. We have also reported the synthesis of Dendron-functionalised MWNT which internalised siRNA in vitro [2]. In this study we demonstrate how a newly synthesized series of polycationic dendron-MWNT constructs with a precisely tailored number of amino-functions (dendron generations) can complex and effectively deliver double stranded siRNA to achieve gene silencing in vitro. A systematic comparison between the f-MWNT series in terms of cellular uptake, cytotoxicity and siRNA complexation is offered. Significant improvement in siRNA delivery with the dendron-MWNT conjugates is shown compared to a widely used transfection agent (cationic liposome:siRNA). Moreover, gene silencing activity using two human cell lines and two different siRNA sequences is demonstrated using the f-MWNT:siRNA complexes. The study reveals that through f-MWNT structure-biological function analysis novel nanotube-based siRNA transfer vectors can be designed with minimal cytotoxicity, effective delivery and gene silencing capabilities.
 
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