title: Regulation of angiogenesis through the efficient delivery of microRNAs into endothelial cells using polyamine-coated carbon nanotubes.
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.
authors.affiliation: Bambino Gesù Children's Hospital-IRCCS, Gene Expression-Microarrays Laboratory, Rome, Italy. Electronic address: andrea.masotti@opbg.net.
authors.forename: Andrea
authors.initials: A
authors.lastname: Masotti
authors.affiliation: University/British Heart Foundation Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Miller
authors.affiliation: Bambino Gesù Children's Hospital-IRCCS, Gene Expression-Microarrays Laboratory, Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Celluzzi
authors.affiliation: University/British Heart Foundation Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Rose
authors.affiliation: INFN-Laboratori Nazionali di Frascati, Rome, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Micciulla
authors.affiliation: University/British Heart Foundation Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
authors.forename: Patrick W F
authors.initials: PW
authors.lastname: Hadoke
authors.affiliation: INFN-Laboratori Nazionali di Frascati, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Bellucci
authors.affiliation: University/British Heart Foundation Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Caporali
mesh_terms: D000818:Animals; D042783:Endothelial Cells; D035683:MicroRNAs; D037742:Nanotubes, Carbon; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011073:Polyamines; D011094:Polyethyleneimine
chemical_list: D035683:MicroRNAs; D037742:Nanotubes, Carbon; D011073:Polyamines; D011094:Polyethyleneimine
keywords: Angiogenesis; Carbon nanotube; Endothelial cell; MicroRNA; Polyamine