Abstract
MicroRNAs (miRNAs) directly regulate gene expression at a post-transcriptional level and represent an attractive therapeutic target for a wide range of diseases. Here, we report a novel strategy for delivering miRNAs to endothelial cells (ECs) to regulate angiogenesis, using polymer functionalized carbon nanotubes (CNTs). CNTs were coated with two different polymers, polyethyleneimine (PEI) or polyamidoamine dendrimer (PAMAM), followed by conjugation of miR-503 oligonucleotides as recognized regulators of angiogenesis. We demonstrated a reduced toxicity for both polymer-coated CNTs, compared with pristine CNTs or polymers alone. Moreover, polymer-coated CNT stabilized miR-503 oligonucleotides and allowed their efficient delivery to ECs. The functionality of PAMAM-CNT-miR-503 complexes was further demonstrated in ECs through regulation of target genes, cell proliferation and angiogenic sprouting and in a mouse model of angiogenesis. This comprehensive series of experiments demonstrates that the use of polyamine-functionalized CNTs to deliver miRNAs is a novel and effective means to regulate angiogenesis.
Highlights
Presentation of work at: Nanotechnologies in Drug Delivery Congress, 27-28 April 2015, London, UK with an oral contribution entitled “Polyamine-coated carbon nanotubes allow efficient microRNAs delivery in endothelial cells”
We demonstrate that coating of carbon nanotubes (CNTs) with PEI or polyamidoamine dendrimer (PAMAM) polymers is an effective means to deliver miRNAs into endothelial cells (ECs)
We showed that polymercoated CNTs conjugated with pre-miR-503 or anti-miR-503 are able to regulate cell proliferation and in vitro angiogenesis through the modification of their target genes
Summary
Presentation of work at: Nanotechnologies in Drug Delivery Congress, 27-28 April 2015, London, UK with an oral contribution entitled “Polyamine-coated carbon nanotubes allow efficient microRNAs delivery in endothelial cells”. We demonstrate that PAMAM-coated CNTs increase the stability of miR-503 oligonucleotides and, regulate target gene expression and angiogenesis in vivo.
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