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Effects of the nanostructure of dendrimer/DNA complexes on their endocytosis and gene expression

Paper ID Volume ID Publish Year Pages File Format Full-Text
9512 633 2010 11 PDF Available
Title
Effects of the nanostructure of dendrimer/DNA complexes on their endocytosis and gene expression
Abstract

Cationic dendrimers constitute a potential nonviral vector for gene therapy due to their ability of forming electrostatic complexes with DNA (dendriplexes). However, the supramolecular structure of dendriplexes and its impact on the cellular uptake and gene transfection remain largely unknown. Using synchrotron small angle X-ray scattering, here we show that DNA in complexes with poly(amidoamine) (PAMAM) G4 dendrimers exhibited three distinct packaging states modulated by the degree of their protonation (dp). Our structure characterization suggests that the nanostructure of DNA in dendriplexes transformed from square-packed straightened chains (dp/0.1) to hexagonally-packed superhelices (dp/0.3) and eventually to a beads-on-string configuration (dp/0.6 and dp/0.9). The transfection efficiency in HT1080 cells significantly enhanced when the dp value was increased from 0.1 to 0.3. This enhancement was due to a higher positive surface charge of dendriplexes formed at higher dp, which facilitated adherence of test dendriplexes to the negatively charged cell membranes for the subsequent endocytosis. Although the surface charge of dendriplexes still increased accordingly, further increase of the dendrimer dp value to 0.9 reduced the transfection efficiency. This unexpected suppression of transfection may be attributed to the wrapping of DNA around dendrimers that frustrates the interaction between dendrimer and cholesterol in the membrane raft via the caveola-mediated endocytosis. These results can be used for the rational design of dendrimer-based gene delivery devices.

Keywords
Nonviral vector; Gene therapy; Synchrotron small angle X-ray scattering; Cellular uptake; Transfection efficiency
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Effects of the nanostructure of dendrimer/DNA complexes on their endocytosis and gene expression
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 31, Issue 21, July 2010, Pages 5660–5670
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