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Mechanism of Enhanced Cellular Uptake and Cytosolic Retention of MK2 Inhibitory Peptide Nano-polyplexes

Overview of attention for article published in Cellular and Molecular Bioengineering, June 2016
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About this Attention Score

  • Good Attention Score compared to outputs of the same age (67th percentile)
  • Good Attention Score compared to outputs of the same age and source (76th percentile)

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5 tweeters
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1 Facebook page

Citations

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17 Dimensions

Readers on

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19 Mendeley
Title
Mechanism of Enhanced Cellular Uptake and Cytosolic Retention of MK2 Inhibitory Peptide Nano-polyplexes
Published in
Cellular and Molecular Bioengineering, June 2016
DOI 10.1007/s12195-016-0446-7
Pubmed ID
Authors

Kameron V. Kilchrist, Brian C. Evans, Colleen M. Brophy, Craig L. Duvall

Abstract

Electrostatic complexation of a cationic MAPKAP kinase 2 inhibitory (MK2i) peptide with the anionic, pH-responsive polymer poly(propylacrylic acid) (PPAA) yields MK2i nano-polyplexes (MK2i-NPs) that significantly increase peptide uptake and intracellular retention. This study focused on elucidating the mechanism of MK2i-NP cellular uptake and intracellular trafficking in vascular smooth muscle cells. Small molecule inhibition of various endocytic pathways showed that MK2i-NP cellular uptake involves both macropinocytosis and clathrin mediated endocytosis, whereas the free peptide exclusively utilizes clathrin mediated endocytosis for cell entry. Scanning electron microscopy studies revealed that MK2i-NPs, but not free MK2i peptide, induce cellular membrane ruffling consistent with macropinocytosis. TEM confirmed that MK2i-NPs induce macropinosome formation and achieve MK2i endo-lysosomal escape and cytosolic delivery. Finally, a novel technique based on recruitment of Galectin-8-YFP was utilized to demonstrate that MK2i-NPs cause endosomal disruption within 30 minutes of uptake. These new insights on the relationship between NP physicochemical properties and cellular uptake and trafficking can potentially be applied to further optimize the MK2i-NP system and more broadly toward the rational engineering of nano-scale constructs for the intracellular delivery of biologic drugs.

Twitter Demographics

The data shown below were collected from the profiles of 5 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 19 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 19 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 9 47%
Student > Master 2 11%
Student > Bachelor 2 11%
Other 1 5%
Lecturer > Senior Lecturer 1 5%
Other 1 5%
Unknown 3 16%
Readers by discipline Count As %
Engineering 4 21%
Chemistry 3 16%
Biochemistry, Genetics and Molecular Biology 2 11%
Pharmacology, Toxicology and Pharmaceutical Science 2 11%
Medicine and Dentistry 1 5%
Other 3 16%
Unknown 4 21%

Attention Score in Context

This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 May 2019.
All research outputs
#3,980,014
of 13,710,419 outputs
Outputs from Cellular and Molecular Bioengineering
#66
of 303 outputs
Outputs of similar age
#82,510
of 262,225 outputs
Outputs of similar age from Cellular and Molecular Bioengineering
#4
of 17 outputs
Altmetric has tracked 13,710,419 research outputs across all sources so far. This one has received more attention than most of these and is in the 70th percentile.
So far Altmetric has tracked 303 research outputs from this source. They receive a mean Attention Score of 2.6. This one has done well, scoring higher than 77% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 262,225 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 67% of its contemporaries.
We're also able to compare this research output to 17 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 76% of its contemporaries.