Enhanced cellular internalization and gene silencing with a series of cationic dendron-multiwalled carbon nanotube:siRNA complexes.
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.
Al-Jamal
Khuloud T
KT
Centre for Drug Delivery Research, School of Pharmacy, University of London, London, UK.
Toma
Francesca M
FM
Yilmazer
Açelya
A
Ali-Boucetta
Hanene
H
Nunes
Antonio
A
Herrero
Maria-Antonia
MA
Tian
Bowen
B
Eddaoudi
Ayad
A
Eddaoui
Ayad
A
Al-Jamal
Wafa' T
WT
Bianco
Alberto
A
Prato
Maurizio
M
Kostarelo
Kostas
K
D001692:Biological Transport / Q000187:drug effects; D002412:Cations / Q000737:chemistry; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival; D020868:Gene Silencing / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D037742:Nanotubes, Carbon / Q000737:chemistry; D034741:RNA, Small Interfering / Q000494:pharmacology*; D014162:Transfection
D002412:Cations; D037742:Nanotubes, Carbon; D034741:RNA, Small Interfering