期刊
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
卷 12, 期 6, 页码 1511-1522出版社
ELSEVIER
DOI: 10.1016/j.nano.2016.02.017
关键词
MicroRNA; Endothelial cell; Carbon nanotube; Polyamine; Angiogenesis
资金
- British Heart Foundation (BHF) [FS/11/52/29018]
- Italian Ministry of Health (Progetto Ricerca Finalizzata) [PE-2011-02347026]
- British Heart Foundation Programme Grant [RG/10/9/28286]
- British Heart Foundation
- Wellcome Trust
- SfP NATO Development of Biosensors using Carbon Nanotubes [SfP - 984537]
- British Heart Foundation [FS/11/52/29018, RG/10/9/28286] Funding Source: researchfish
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. (C) 2016 The Authors. Published by Elsevier Inc.
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