Document Detail


The role of cytoskeleton networks on lipid-mediated delivery of DNA.
MedLine Citation:
PMID:  23343159     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Lipid-mediated delivery of DNA is hindered by extracellular and intracellular barriers that significantly reduce the transfection efficiency of synthetic nonviral vectors.
RESULTS: In this study we investigated the role of the actin and microtubule networks on the uptake and cytoplasmic transport of multicomponent cationic liposome-DNA complexes in CHO-K1 live cells by means of confocal laser scanning microscopy and 3D single particle tracking. Treatment with actin (latrunculin B)- and microtubule-disrupting (nocodazole) reagents indicated that intracellular trafficking of complexes predominantly involves microtubule-dependent active transport. We found that the actin network has a major effect on the initial uptake of complexes, while the microtubule network is mainly responsible for the subsequent active transportation to the lysosomes.
CONCLUSION: Collectively, a strategy to improve the efficiency of lipid gene vectors can be formulated. We could find a lipid formulation that allows the nanoparticles to avoid the microtubule pathway to lysosomes.
Authors:
Stefano Coppola; Francesco Cardarelli; Daniela Pozzi; Laura C Estrada; Michelle A Digman; Enrico Gratton; Angelo Bifone; Carlotta Marianecci; Giulio Caracciolo
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Therapeutic delivery     Volume:  4     ISSN:  2041-5990     ISO Abbreviation:  Ther Deliv     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-24     Completed Date:  2013-03-07     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  101538870     Medline TA:  Ther Deliv     Country:  England    
Other Details:
Languages:  eng     Pagination:  191-202     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Actins / metabolism*
Animals
Bicyclo Compounds, Heterocyclic / pharmacology
Biological Transport, Active
CHO Cells
Cations
Cricetinae
Cricetulus
Cytoplasm / metabolism
Cytoskeleton / metabolism
DNA / administration & dosage*,  pharmacokinetics
Lipids / chemistry*
Liposomes
Microscopy, Confocal
Microtubules / metabolism*
Nocodazole / pharmacology
Thiazolidines / pharmacology
Transfection
Grant Support
ID/Acronym/Agency:
5P41RR003155/RR/NCRR NIH HHS; 5P50 GM076516/GM/NIGMS NIH HHS; 8P41GM103540/GM/NIGMS NIH HHS; P41 GM103540/GM/NIGMS NIH HHS; P41 RR003155/RR/NCRR NIH HHS; P50 GM076516/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Actins; 0/Bicyclo Compounds, Heterocyclic; 0/Cations; 0/Lipids; 0/Liposomes; 0/Thiazolidines; 76343-94-7/latrunculin B; 9007-49-2/DNA; SH1WY3R615/Nocodazole
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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