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Albumin pre-coating enhances intracellular siRNA delivery of multifunctional amphiphile/siRNA nanoparticles

Authors Kummitha CM, Malamas, Lu Z

Received 26 May 2012

Accepted for publication 26 June 2012

Published 2 October 2012 Volume 2012:7 Pages 5205—5214


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China M Kummitha, Anthony S Malamas, Zheng-Rong Lu

Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA

Abstract: Nonspecific association of serum molecules with short-interfering RNA (siRNA) nanoparticles can change their physiochemical characteristics, and results in reduced cellular uptake in the target tissue during the systemic siRNA delivery process. Serum albumin is the most abundant protein in the body and has been used to modify the surface of nanoparticles, to inhibit association of other serum molecules. Here, we hypothesized that surface modification of lipid-based nanoparticular siRNA delivery systems with albumin could prevent their interaction with serum proteins, and improve intracellular uptake. In this study, we investigated the influence of albumin on the stability and intracellular siRNA delivery of the targeted siRNA nanoparticles of a polymerizable and pH-sensitive multifunctional surfactant N-(1-aminoethyl)iminobis[N-(oleoylcysteinylhistinyl-1-aminoethyl)propionamide] (EHCO) in serum. Serum resulted in a significant increase in the size of targeted EHCO/siRNA nanoparticles and inhibited cellular uptake of the nanoparticles. Coating of targeted EHCO/siRNA nanoparticles with bovine serum albumin at 9.4 µM prior to cell transfection improved cellular uptake and gene silencing efficacy of EHCO/siRNA targeted nanoparticles in serum-containing media, as compared with the uncoated nanoparticles. At a proper concentration, albumin has the potential to minimize interactions of serum proteins with siRNA nanoparticles for effective systemic in vivo siRNA delivery.

Keywords: multifunctional, lipid nanoparticles, RNA interference, pH-sensitive amphiphile, siRNA

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