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

Al-Jamal, K.T., Toma, F.M., Yilmazer, A., Ali-Boucetta, H., Nunes, A., Herrero, M-A., Tian, B., Eddaoudi, A., Al-Jamal, W.T., Bianco, A., Prato, M. and Kostarelos, K. (2010) Enhanced cellular internalization and gene silencing with a series of cationic dendron-multiwalled carbon nanotube:siRNA complexes. FASEB Journal, 24 (11). pp. 4354-4365. 10.1096/fj.09-141036.

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DOI: 10.1096/fj.09-141036

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 proposed as novel nanomaterials that can offer significant advantages for the intracellular delivery of nucleic acids, such as siRNA. We recently demonstrated in a proof-of-principle study that amino-functionalized multiwalled 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. In the present 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, and gene silencing was obtained in 2 human cell lines using 2 different siRNA sequences. The study reveals that through f-MWNT structure-biological function analysis novel nanotube-based siRNA transfer vectors can be designed with minimal cytotoxicity and effective delivery and gene-silencing capabilities

Item Type:Article
Uncontrolled Keywords:Gene transfer; Interference; Knockdown; Nanotechnology; Nonviral; RNA
Departments, units and centres:Department of Pharmaceutics > Department of Pharmaceutics
ID Code:2845
Journal or Publication Title:FASEB Journal
Deposited By:Library Staff
Deposited On:24 Feb 2012 11:48
Last Modified:24 Feb 2012 11:48

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