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Enhanced siRNA delivery into cells by exploiting the synergy between targeting ligands and cell-penetrating peptides

Paper ID Volume ID Publish Year Pages File Format Full-Text
7394 551 2011 10 PDF Available
Title
Enhanced siRNA delivery into cells by exploiting the synergy between targeting ligands and cell-penetrating peptides
Abstract

We have developed a polymer nanoparticle-based siRNA delivery system that exploits a cell surface binding synergism between targeting ligands and cell-penetrating peptides. Nanoparticles were coated with folate and penetratin via a PEGylated phospholipid linker (DSPE-PEG): the combination of both of these ligands represents a strategy for enhancing intracellular delivery of attached polymer nanoparticles. Nanoparticles were characterized for size, morphology, density of surface modification, and ligand association and retention. The surface coverage achieved on DSPE-PEG-coated nanoparticles is as high as (or higher than) obtained with other ligand-modified nano-scale particulate systems (∼0.5–5 pmol ligand/cm2). Additionally, these nanoparticles were loaded with a high density of siRNA (∼130–140 pmol siRNA/mg nanoparticles), which is slowly released upon incubation in water. Synergies between the activity of surface binding and cell internalizing ligands on these siRNA-loaded nanoparticles impart delivery enhancements that improve their gene silencing efficacy both in culture and in tumor models. Traditionally, targeting ligands function by binding to cell surface receptors, while cell-penetrating peptides function by nonspecifically transporting across cell membranes. Interestingly, we have observed that improved delivery of these dual-functionalized nanoparticles was in part, a result of increased cell surface avidity afforded by both ligands. This siRNA delivery system presents an approach to surface modification of nanovehicles, in which multiple ligands function in parallel to enhance cell binding and uptake.

Keywords
Nanoparticle; Copolymer; Gene therapy; Phospholipid; Drug delivery; Controlled drug release
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Enhanced siRNA delivery into cells by exploiting the synergy between targeting ligands and cell-penetrating peptides
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 32, Issue 26, September 2011, Pages 6194–6203
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us