Virus-Sized DNA Nanoparticles for Gene Delivery Based on Micelles of Cationic Calixarenes
Macrocyclic amphiphilic molecules based on calix[4]arenes are highly attractive for controlled supramolecular assembly of DNA into small nanoparticles, since they present a unique conical architecture and can bear multiple charged groups. In the present work, we synthesized new amphiphilic calixaren...
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Published in | Chemistry : a European journal Vol. 17; no. 20; pp. 5526 - 5538 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Weinheim
WILEY-VCH Verlag
09.05.2011
WILEY‐VCH Verlag Wiley Wiley Subscription Services, Inc Wiley-VCH Verlag |
Subjects | |
Online Access | Get full text |
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Summary: | Macrocyclic amphiphilic molecules based on calix[4]arenes are highly attractive for controlled supramolecular assembly of DNA into small nanoparticles, since they present a unique conical architecture and can bear multiple charged groups. In the present work, we synthesized new amphiphilic calixarenes bearing cationic groups at the upper rim and alkyl chains at the lower rim. Their self‐assembly in aqueous solution was characterized by fluorescent probes, fluorescence correlation spectroscopy, dynamic light scattering, gel electrophoresis and atomic force microscopy. We found that calixarenes bearing long alkyl chains (octyl) self‐assemble into micelles of 6 nm diameter at low critical micellar concentration and present the unique ability to condense DNA into small nanoparticles of about 50 nm diameter. In contrast, the short‐chain (propyl) analogues that cannot form micelles at low concentrations failed to condense DNA, giving large polydisperse DNA complexes. Thus, formation of small DNA nanoparticles is hierarchical, requiring assembly of calixarenes into micellar building blocks that further co‐assemble with DNA into small virus‐sized particles. The latter showed much better gene transfection efficiency in cell cultures relative to the large DNA complexes with the short‐chain analogues, which indicates that gene delivery of calixarene/DNA complexes depends strongly on their structure. Moreover, all cationic calixarenes studied showed low cytotoxicity. Thus, this work presents a two‐step hierarchical assembly of small DNA nanoparticles for gene delivery based on amphiphilic cone‐shaped cationic calixarenes.
Calixarene/DNA nanoparticles: Cone‐shaped cationic amphiphilic calixarenes synthesized in this work form micelles of 6 nm diameter that can compact DNA into small nanoparticles of about 50 nm diameter (see figure; scale bar=1 μm). These virus‐sized particles showed promising transfection properties and low cytotoxicity in cell culture and therefore can be of interest for the development of new gene delivery vectors. |
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Bibliography: | ArticleID:CHEM201100154 Fondation pour la Recherche Médicale (FRM) istex:9ABF713FBDE8B5E566682DA880DF946832A0B810 ark:/67375/WNG-WDV3ZR5M-9 These authors contributed equally to this work ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0947-6539 1521-3765 1521-3765 |
DOI: | 10.1002/chem.201100154 |