Regulation of angiogenesis through the efficient delivery of microRNAs into endothelial cells using polyamine-coated carbon nanotubes

Andrea Masotti, Mark R. Miller, Antonella Celluzzi, Lorraine Rose, Federico Micciulla, Patrick W.F. Hadoke, Stefano Bellucci, Andrea Caporali

Research output: Contribution to journalArticlepeer-review

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 furthermore, 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.
Original languageEnglish
Pages (from-to)1511–1522
Number of pages32
JournalNanomedicine: Nanotechnology, Biology and Medicine
Volume12
Issue number6
Early online date22 Mar 2016
DOIs
Publication statusPublished - Aug 2016

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