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Multi-layered nanoparticles for penetrating the endosome and nuclear membrane via a step-wise membrane fusion process

Paper ID Volume ID Publish Year Pages File Format Full-Text
10088 663 2009 10 PDF Available
Title
Multi-layered nanoparticles for penetrating the endosome and nuclear membrane via a step-wise membrane fusion process
Abstract

Efficient targeting of DNA to the nucleus is a prerequisite for effective gene therapy. The gene-delivery vehicle must penetrate through the plasma membrane, and the DNA-impermeable double-membraned nuclear envelope, and deposit its DNA cargo in a form ready for transcription. Here we introduce a concept for overcoming intracellular membrane barriers that involves step-wise membrane fusion. To achieve this, a nanotechnology was developed that creates a multi-layered nanoparticle, which we refer to as a Tetra-lamellar Multi-functional Envelope-type Nano Device (T-MEND). The critical structural elements of the T-MEND are a DNA-polycation condensed core coated with two nuclear membrane-fusogenic inner envelopes and two endosome-fusogenic outer envelopes, which are shed in stepwise fashion. A double-lamellar membrane structure is required for nuclear delivery via the stepwise fusion of double layered nuclear membrane structure. Intracellular membrane fusions to endosomes and nuclear membranes were verified by spectral imaging of fluorescence resonance energy transfer (FRET) between donor and acceptor fluorophores that had been dually labeled on the liposome surface. Coating the core with the minimum number of nucleus-fusogenic lipid envelopes (i.e., 2) is essential to facilitate transcription. As a result, the T-MEND achieves dramatic levels of transgene expression in non-dividing cells.

Keywords
Nuclear delivery; Gene delivery; Intracellular trafficking; Membrane fusion; Multi-coating
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Multi-layered nanoparticles for penetrating the endosome and nuclear membrane via a step-wise membrane fusion process
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 30, Issue 15, May 2009, Pages 2940–2949
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