Document Detail


Effect of Polyplex Morphology on Cellular Uptake, Intracellular Trafficking, and Transgene Expression.
MedLine Citation:
PMID:  24195594     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Nanoparticle morphology has been shown to affect cellular uptake, but there are few studies investigating the impact of particle shape on biologic drug delivery. Recently, our group synthesized a series of N-(2-hydroxypropyl) methacrylamide (HPMA)-oligolysine brush polymers for nucleic acid delivery that varied in oligolysine peptide length and polymer molecular weight. Interestingly, a 50% longer peptide (K15) transfected very poorly compared to the optimized polymer comprised of K10 peptide despite similar chemical composition and molecular weight. We hypothesized that differences in particle morphology contributed to the differences in plasmid DNA delivery. We found that particles formed with plasmid DNA and a polymer with the longer oligolysine peptide (pHK15) had larger aspect ratios than particles formed with optimized polymer (pHK10). Even though both formulations showed similar percentages of cellular association, particles of a higher aspect ratio were internalized to a lesser extent. Furthermore, the rod-like particles accumulated more in endosomal/lysosomal compartments, leading to delayed nuclear delivery. Other parameters, such as particle surface charge, unpackaging ability, uptake mechanism, intracellular trafficking, nor the presence of heparan sulfate proteoglycans did not significantly differ between the two polymer formulations. These results indicate that, for this system, polyplex morphology primarily impacts nucleic acid delivery efficiency through differences in cellular internalization rates.
Authors:
Julie Shi; Jennifer L Choi; Brian Chou; Russell N Johnson; Joan G Schellinger; Suzie H Pun
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-11-6
Journal Detail:
Title:  ACS nano     Volume:  -     ISSN:  1936-086X     ISO Abbreviation:  ACS Nano     Publication Date:  2013 Nov 
Date Detail:
Created Date:  2013-11-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101313589     Medline TA:  ACS Nano     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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