Issue 48, 2021

Controlled delivery of gold nanoparticle-coupled miRNA therapeutics via an injectable self-healing hydrogel

Abstract

Differential expression of microRNAs (miRNAs) plays a role in many diseases, including cancer and cardiovascular diseases. Potentially, miRNAs could be targeted with miRNA-therapeutics. Sustained delivery of these therapeutics remains challenging. This study couples miR-mimics to PEG-peptide gold nanoparticles (AuNP) and loads these AuNP-miRNAs in an injectable, shear thinning, self-assembling polymer nanoparticle (PNP) hydrogel drug delivery platform to improve delivery. Spherical AuNPs coated with fluorescently labelled miR-214 are loaded into an HPMC-PEG-b-PLA PNP hydrogel. Release of AuNP/miRNAs is quantified, AuNP-miR-214 functionality is shown in vitro in HEK293 cells, and AuNP-miRNAs are tracked in a 3D bioprinted human model of calcific aortic valve disease (CAVD). Lastly, biodistribution of PNP-AuNP-miR-67 is assessed after subcutaneous injection in C57BL/6 mice. AuNP-miRNA release from the PNP hydrogel in vitro demonstrates a linear pattern over 5 days up to 20%. AuNP-miR-214 transfection in HEK293 results in 33% decrease of Luciferase reporter activity. In the CAVD model, AuNP-miR-214 are tracked into the cytoplasm of human aortic valve interstitial cells. Lastly, 11 days after subcutaneous injection, AuNP-miR-67 predominantly clears via the liver and kidneys, and fluorescence levels are again comparable to control animals. Thus, the PNP-AuNP-miRNA drug delivery platform provides linear release of functional miRNAs in vitro and has potential for in vivo applications.

Graphical abstract: Controlled delivery of gold nanoparticle-coupled miRNA therapeutics via an injectable self-healing hydrogel

Supplementary files

Article information

Article type
Paper
Submitted
30 Jul 2021
Accepted
21 Oct 2021
First published
24 Nov 2021
This article is Open Access
Creative Commons BY-NC license

Nanoscale, 2021,13, 20451-20461

Controlled delivery of gold nanoparticle-coupled miRNA therapeutics via an injectable self-healing hydrogel

C. F. T. van der Ven, M. W. Tibbitt, J. Conde, A. van Mil, J. Hjortnaes, P. A. Doevendans, J. P. G. Sluijter, E. Aikawa and R. S. Langer, Nanoscale, 2021, 13, 20451 DOI: 10.1039/D1NR04973A

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