Back to Journals » International Journal of Nanomedicine » Volume 8 » Issue 1

Targeting miRNA-based medicines to cystic fibrosis airway epithelial cells using nanotechnology

Authors McKiernan PJ, Cunningham O, Greene CM, Cryan SA

Received 2 May 2013

Accepted for publication 9 July 2013

Published 11 October 2013 Volume 2013:8(1) Pages 3907—3915

DOI https://doi.org/10.2147/IJN.S47551

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Paul J McKiernan,2 Orla Cunningham,1,2 Catherine M Greene,2 Sally-Ann Cryan1,3

1
School of Pharmacy, Royal College of Surgeons in Ireland, 2Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland Education and Research Centre, Beaumont Hospital, 3Trinity Centre for Bioengineering, Trinity College Dublin, Dublin, Ireland

Abstract: Cystic fibrosis (CF) is an inherited disorder characterized by chronic airway inflammation. microRNAs (miRNAs) are endogenous small RNAs which act on messenger (m)RNA at a post transcriptional level, and there is a growing understanding that altered expression of miRNA is involved in the CF phenotype. Modulation of miRNA by replacement using miRNA mimics (premiRs) presents a new therapeutic paradigm for CF, but effective and safe methods of delivery to the CF epithelium are limiting clinical translation. Herein, polymeric nanoparticles are investigated for delivery of miRNA mimics into CF airway epithelial cells, using miR-126 as a proof-of-concept premiR cargo to determine efficiency. Two polymers, polyethyleneimine (PEI) and chitosan, were used to prepare miRNA nanomedicines, characterized for their size, surface (zeta) potential, and RNA complexation efficiency, and screened for delivery and cytotoxicity in CFBE41o- (human F508del cystic fibrosis transmembrane conductance regulator bronchial epithelial) cells using a novel high content analysis method. RNA extraction was carried out 24 hours post transfection, and miR-126 and TOM1 (target of Myb1) expression (a validated miR-126 target) was assessed. Manufacture was optimized to produce small nanoparticles that effectively complexed miRNA. Using high content analysis, PEI-based nanoparticles were more effective than chitosan-based nanoparticles in facilitating uptake of miRNA into CFBE41o- cells and this was confirmed in miR-126 assays. PEI-premiR-126 nanoparticles at low nitrogen/phosphate (N/P) ratios resulted in significant knockdown of TOM1 in CFBE41o- cells, with the most significant reduction of 66% in TOM1 expression elicited at an N/P ratio of 1:1 while chitosan-based miR-126 nanomedicines failed to facilitate statistically significant knockdown of TOM1 and both nanoparticles appeared relatively nontoxic. miRNA nanomedicine uptake can be qualitatively and quantitatively assessed rapidly by high content analysis and is highly polymer-dependent but, interestingly, there is not a direct correlation between the levels of miRNA uptake and the downstream gene knockdown. Polymeric nanoparticles can deliver premiRs effectively to CFBEs in order to modulate gene expression but must be tailored specifically for miRNA delivery.

Keywords: miR-126, nanotechnology, cystic fibrosis, TOM1, high content analysis, inflammation

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]

 

Readers of this article also read:

Intradermal air pouch leukocytosis as an in vivo test for nanoparticles

Vandooren J, Berghmans N, Dillen C, Van Aelst I, Ronsse I, Israel LL, Rosenberger I, Kreuter J, Lellouche JP, Michaeli S, Locatelli E, Comes Franchini M, Aiertza MK, Sánchez-Abella L, Loinaz I, Edwards DR, Shenkman L, Opdenakker G

International Journal of Nanomedicine 2013, 8:4745-4756

Published Date: 13 December 2013

Synthesis and characterization of surface-enhanced Raman-scattered gold nanoparticles

Kalmodia S, Harjwani J, Rajeswari R, Yang W, Barrow CJ, Ramaprabhu S, Krishnakumar S, Elchuri SV

International Journal of Nanomedicine 2013, 8:4327-4338

Published Date: 6 November 2013

A peptide-mediated targeting gene delivery system for malignant glioma cells

Wang C, Ning L, Wang H, Lu Z, Li X, Fan X, Wang X, Liu Y

International Journal of Nanomedicine 2013, 8:3631-3640

Published Date: 24 September 2013

Combined efficacy of biologically synthesized silver nanoparticles and different antibiotics against multidrug-resistant bacteria

Naqvi SZ, Kiran U, Ali MI, Jamal A, Hameed A, Ahmed S, Ali N

International Journal of Nanomedicine 2013, 8:3187-3195

Published Date: 20 August 2013

Magnetic nanoparticles of Fe3O4 enhance docetaxel-induced prostate cancer cell death

Sato A, Itcho N, Ishiguro H, Okamoto D, Kobayashi N, Kawai K, Kasai H, Kurioka D, Uemura H, Kubota Y, Watanabe M

International Journal of Nanomedicine 2013, 8:3151-3160

Published Date: 19 August 2013

Cisplatin-incorporated nanoparticles of poly(acrylic acid-co-methyl methacrylate) copolymer

Lee KD, Jeong YI, Kim DH, Lim GT, Choi KC

International Journal of Nanomedicine 2013, 8:2835-2845

Published Date: 8 August 2013