Targeted Sterically Stabilized Phospholipid siRNA.... Renal Fibrosis.pdf (3.62 MB)

Targeted sterically stabilized phospholipid siRNA nanomedicine for hepatic and renal fibrosis

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journal contribution
posted on 27.06.2016 by F. Khaja, D. Jayawardena, A. Kuzmis, H. Önyüksel
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.


This work was supported in part by the University of Illinois Office of Technology Management Proof of Concept Gap-funding Initiative DE108 (HO). FK training was supported by the American Foundation for Pharmaceutical Education (AFPE) fellowship and the Chicago Biomedical Consortium (CBC) Scholarship. Most of the work was conducted in a facility constructed with support from Research Facilities Improvement Grant CO6RR15482 from the National Center for Research Resources, National Institutes of Health (NIH).


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This is a copy of an article published in the Nanomaterials. © 2016 by the author(s).







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