| Polymeric Nucleic Acid Vehicles Exploit Active Inter-Organelle Trafficking Mechanisms. | |
| | |
MedLine Citation:
|
PMID: 23234474 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Materials that self-assemble with nucleic acids into nanocomplexes (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 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 (ODNs) to the Golgi and endoplasmic reticulum, which may be a route taken for nuclear delivery. However, Glycofect polyplexes demonstrated higher colocalization with the ER than PEI polyplexes and colocalization experiments indicate 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 |
Related Documents
:
|
23609414 - Interactions between oil substrates and glucose on pure cultures of ruminal lipase-prod... 22981414 - Maternal intake of omega-3 essential fatty acids improves long term potentiation in the... 23218274 - Effects of lipids on enzymatic hydrolysis and physical properties of starch. 18453694 - Structures of the human ceramide activator protein saposin d. 3949784 - Amino acid sequence of myoglobin from the mollusc dolabella auricularia. 18212744 - Retinoic acid downregulates rae1 leading to apc(cdh1) activation and neuroblastoma sh-s... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2012-12-12 |
Journal Detail:
|
Title: ACS nano Volume: - ISSN: 1936-086X ISO Abbreviation: ACS Nano Publication Date: 2012 Dec |
Date Detail:
|
Created Date: 2012-12-13 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 101313589 Medline TA: ACS Nano Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Code Red and Blue - Safely Limiting Health Care's GDP Footprint.
Next Document: Charge state of lysozyme molecules in the gas phase produced by IR-laser ablation of droplet beam.