Document Detail


Polymeric nucleic acid vehicles exploit active interorganelle trafficking mechanisms.
MedLine Citation:
PMID:  23234474     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Materials that self-assemble with nucleic acids into nanocomplexes (e.g. polyplexes) are widely used in many fundamental biological and biomedical experiments. However, understanding the intracellular transport mechanisms of these vehicles remains a major hurdle in their effective usage. Here, we investigate two polycation models, Glycofect (which slowly degrades via hydrolysis) and linear polyethyleneimine (PEI) (which does not rapidly hydrolyze), to determine the impact of polymeric structure on intracellular trafficking. Cells transfected using Glycofect underwent increasing transgene expression over the course of 40 h and remained benign over the course of 7 days. Transgene expression in cells transfected with PEI peaked at 16 h post-transfection and resulted in less than 10% survival after 7 days. While saccharide-containing Glycofect has a higher buffering capacity than PEI, polyplexes created with Glycofect demonstrate more sustained endosomal release, possibly suggesting an additional or alternative delivery mechanism to the classical "proton sponge mechanism". PEI appeared to promote release of DNA from acidic organelles more than Glycofect. Immunofluorescence images indicate that both Glycofect and linear PEI traffic oligodeoxynucleotides to the Golgi and endoplasmic reticulum, which may be a route towards nuclear delivery. However, Glycofect polyplexes demonstrated higher co-localization with the ER than PEI polyplexes, and co-localization experiments indicate the retrograde transport of polyplexes via COP I vesicles from the Golgi to the ER. We conclude that slow release and unique trafficking behaviors of Glycofect polyplexes may be due to the presence of saccharide units and the degradable nature of the polymer, allowing more efficacious and benign delivery.
Authors:
Katye M Fichter; Nilesh P Ingle; Patrick M McLendon; Theresa M Reineke
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-12-31
Journal Detail:
Title:  ACS nano     Volume:  7     ISSN:  1936-086X     ISO Abbreviation:  ACS Nano     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-22     Completed Date:  2013-06-27     Revised Date:  2014-03-21    
Medline Journal Info:
Nlm Unique ID:  101313589     Medline TA:  ACS Nano     Country:  United States    
Other Details:
Languages:  eng     Pagination:  347-64     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
DNA / pharmacokinetics*
Molecular Imaging / methods*
Muscle Cells / cytology,  metabolism*
Nanocapsules / chemistry*
Organelles / metabolism*
Rats
Transfection / methods*
Grant Support
ID/Acronym/Agency:
1-R21-EB3938-01/EB/NIBIB NIH HHS; DP2 OD006669/OD/NIH HHS; DP2-OD006669-01/OD/NIH HHS; R21 EB003938/EB/NIBIB NIH HHS
Chemical
Reg. No./Substance:
0/Nanocapsules; 9007-49-2/DNA
Comments/Corrections

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