In Vivo Gene-Silencing in Fibrotic Liver by siRNA-Loaded Cationic Nanohydrogel Particles

Leonard Kaps; Lutz Nuhn; Misbah Aslam; Alexander Brose; Friedrich Foerster; Sebastian Rosigkeit; Patricia Renz; Rosario Heck; Yong Ook Kim; Ingo Lieberwirth; Detlef Schuppan; Rudolf Zentel

doi:10.1002/adhm.201500826

In Vivo Gene-Silencing in Fibrotic Liver by siRNA-Loaded Cationic Nanohydrogel Particles

Adv Healthc Mater. 2015 Dec 30;4(18):2809-15. doi: 10.1002/adhm.201500826. Epub 2015 Dec 2.

Authors

Leonard Kaps¹, Lutz Nuhn^{2

3}, Misbah Aslam¹, Alexander Brose¹, Friedrich Foerster^{1

4}, Sebastian Rosigkeit¹, Patricia Renz⁵, Rosario Heck¹, Yong Ook Kim¹, Ingo Lieberwirth⁵, Detlef Schuppan^{1

6}, Rudolf Zentel²

Affiliations

¹ Institute of Translational Immunology and Research Center for Immune Therapy (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55101, Mainz, Germany.
² Institute of Organic Chemistry, Johannes Gutenberg-University Mainz, Duesbergweg 10-14, 55128, Mainz, Germany.
³ Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.
⁴ Department of Medicine I (Gastroenterology Hepatology, and Nephrology), University Medical Center of Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55101, Mainz, Germany.
⁵ Max Planck Institute for Polymer Research, Ackermannweg 10, 55128, Mainz, Germany.
⁶ Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA, 02215, USA.

PMID: 26627192
DOI: 10.1002/adhm.201500826

Abstract

Cationic nanohydrogel particles loaded with anti-Col1α1 siRNA suppress collagen synthesis and deposition in fibrotic mice: Systemically administered 40 nm sized nanogel particles accumulate in collagen-expressing cells in the liver. Their siRNA payload induces a sequence specific in vivo gene knockdown affording an efficient antifibrotic effect in mice with liver fibrosis.

Keywords: cationic nanohydrogels; in vivo gene knockdown; liver fibrosis; nanogels; siRNA delivery.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cations
Cell Line
Gene Silencing*
Gene Transfer Techniques
Hydrogels / chemistry*
Liver Cirrhosis / metabolism*
Mice
Nanogels
Nanoparticles / chemistry
Nanoparticles / ultrastructure
Polyethylene Glycols / chemistry*
Polyethyleneimine / chemistry*
RNA, Small Interfering / metabolism*
Tissue Distribution

Substances

Cations
Hydrogels
Nanogels
RNA, Small Interfering
polyethylene glycol polyethyleneimine nanogel
Polyethylene Glycols
Polyethyleneimine