Next Article in Journal
The Influence of Carbonaceous Matrices and Electrocatalytic MnO2 Nanopowders on Lithium-Air Battery Performances
Next Article in Special Issue
Repair of the Orbital Wall Fractures in Rabbit Animal Model Using Nanostructured Hydroxyapatite-Based Implant
Previous Article in Journal
Aqueous Dispersions of Silica Stabilized with Oleic Acid Obtained by Green Chemistry
Previous Article in Special Issue
Effects of Particle Hydrophobicity, Surface Charge, Media pH Value and Complexation with Human Serum Albumin on Drug Release Behavior of Mitoxantrone-Loaded Pullulan Nanoparticles
Article Menu

Export Article

Open AccessFeature PaperArticle
Nanomaterials 2016, 6(1), 8; doi:10.3390/nano6010008

Targeted Sterically Stabilized Phospholipid siRNA Nanomedicine for Hepatic and Renal Fibrosis

Department of Biopharmaceutical Sciences (M/C 865), College of Pharmacy, University of Illinois at Chicago, 833 South Wood St., Chicago, IL 60612-7231, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Andrea Danani
Received: 16 October 2015 / Revised: 23 December 2015 / Accepted: 28 December 2015 / Published: 5 January 2016
(This article belongs to the Special Issue Nanoparticles Assisted Drug Delivery)
View Full-Text   |   Download PDF [4645 KB, uploaded 5 January 2016]   |  

Abstract

Since its discovery, small interfering RNA (siRNA) has been considered a potent tool for modulating gene expression. It has the ability to specifically target proteins via selective degradation of messenger RNA (mRNA) not easily accessed by conventional drugs. Hence, RNA interference (RNAi) therapeutics have great potential in the treatment of many diseases caused by faulty protein expression such as fibrosis and cancer. However, for clinical application siRNA faces a number of obstacles, such as poor in vivo stability, and off-target effects. Here we developed a unique targeted nanomedicine to tackle current siRNA delivery issues by formulating a biocompatible, biodegradable and relatively inexpensive nanocarrier of sterically stabilized phospholipid nanoparticles (SSLNPs). This nanocarrier is capable of incorporating siRNA in its core through self-association with a novel cationic lipid composed of naturally occuring phospholipids and amino acids. This overall assembly protects and delivers sufficient amounts of siRNA to knockdown over-expressed protein in target cells. The siRNA used in this study, targets connective tissue growth factor (CTGF), an important regulator of fibrosis in both hepatic and renal cells. Furthermore, asialoglycoprotein receptors are targeted by attaching the galactosamine ligand to the nanocarries which enhances the uptake of nanoparticles by hepatocytes and renal tubular epithelial cells, the major producers of CTGF in fibrosis. On animals this innovative nanoconstruct, small interfering RNA in sterically stabilized phospholipid nanoparticles (siRNA-SSLNP), showed favorable pharmacokinetic properties and accumulated mostly in hepatic and renal tissues making siRNA-SSLNP a suitable system for targeting liver and kidney fibrotic diseases. View Full-Text
Keywords: siRNA; sterically stabilized phospholipid nanoparticles; galactosamine; hepatic stellate cells; fibrosis siRNA; sterically stabilized phospholipid nanoparticles; galactosamine; hepatic stellate cells; fibrosis
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Khaja, F.; Jayawardena, D.; Kuzmis, A.; Önyüksel, H. Targeted Sterically Stabilized Phospholipid siRNA Nanomedicine for Hepatic and Renal Fibrosis. Nanomaterials 2016, 6, 8.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Nanomaterials EISSN 2079-4991 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top