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Structure-activity relationships of cationic shell-crosslinked knedel-like nanoparticles: Shell composition and transfection efficiency/cytotoxicity

Paper ID Volume ID Publish Year Pages File Format Full-Text
9368 627 2010 9 PDF Available
Title
Structure-activity relationships of cationic shell-crosslinked knedel-like nanoparticles: Shell composition and transfection efficiency/cytotoxicity
Abstract

Cationic nanoparticles are a promising class of transfection agents for oligonucleotide and gene delivery, but vary greatly in their effectiveness and cytotoxicity. Recently, we developed a new class of cationic transfection agents based on cationic shell-crosslinked knedel-like nanoparticles (cSCKs) that efficiently transfect mammalian cells with both oligonucleotides and plasmid DNA. In an effort to further improve transfection efficiency without increasing cytotoxicity, we examined the effects of the composition of primary amine (pa), tertiary amine (ta) and carboxylic acid (ca) groups in the shell of these nanoparticles. A series of discrete complexes of the cSCKs with plasmid DNA (pDNA) or phosphorothioate 2′-OMe oliogonucleotides (ps-MeON) were prepared over a broad range of amine to phosphate ratios (N/P ratio) of 4:1–40:1. The sizes of the complexes and the ability of the nanoparticles to completely bind ODNs were found to depend on the cSCK amine to DNA phosphate (N/P) ratio and the cSCK buffering capacity. The cSCKs were then evaluated for their ability to transfect cells with plasmid DNA by monitoring fluorescence from an encoded EGFP, and for delivery of ps-MeON by monitoring luminescence from luciferase resulting from ps-MeON-mediated splicing correction. Whereas the cationic cSCK-pa25-ta75 was found to be best for transfecting plasmid DNA into HeLa cells at an N/P ratio of 20:1, cSCK-pa50-ta50, at an N/P ratio 10:1 was best for ps-MeON delivery. We also found that increasing the proportion of tertiary relative to primary amine reduced the cytotoxicity. These results demonstrate that a dramatic improvement in gene and oligonucleotide delivery efficiency with decreased cytotoxicity in HeLa cells can be achieved by incorporation of tertiary amines into the shells of cSCKs.

Keywords
Nanoparticle; Gene transfer; Cytotoxicity; Endocytosis; Proton sponge effect; Antisense
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Structure-activity relationships of cationic shell-crosslinked knedel-like nanoparticles: Shell composition and transfection efficiency/cytotoxicity
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 31, Issue 7, March 2010, Pages 1805–1813
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