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Investigation of enzyme-sensitive lipid nanoparticles for delivery of siRNA to blood–brain barrier and glioma cells

Overview of attention for article published in International Journal of Nanomedicine, September 2015
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (83rd percentile)
  • High Attention Score compared to outputs of the same age and source (94th percentile)

Mentioned by

twitter
11 tweeters
patent
1 patent

Citations

dimensions_citation
64 Dimensions

Readers on

mendeley
100 Mendeley
Title
Investigation of enzyme-sensitive lipid nanoparticles for delivery of siRNA to blood–brain barrier and glioma cells
Published in
International Journal of Nanomedicine, September 2015
DOI 10.2147/ijn.s87334
Pubmed ID
Authors

Thomas Andresen, Jonas Bruun, Trine B. Larsen, Rasmus I. Jølck, Rasmus Eliasen, Rene Holm, Torben Gjetting

Abstract

Clinical applications of siRNA for treating disorders in the central nervous system require development of systemic stable, safe, and effective delivery vehicles that are able to cross the impermeable blood-brain barrier (BBB). Engineering nanocarriers with low cellular interaction during systemic circulation, but with high uptake in targeted cells, is a great challenge and is further complicated by the BBB. As a first step in obtaining such a delivery system, this study aims at designing a lipid nanoparticle (LNP) able to efficiently encapsulate siRNA by a combination of titratable cationic lipids. The targeted delivery is obtained through the design of a two-stage system where the first step is conjugation of angiopep to the surface of the LNP for targeting the low-density lipoprotein receptor-related protein-1 expressed on the BBB. Second, the positively charged LNPs are masked with a negatively charged PEGylated (poly(ethylene glycol)) cleavable lipopeptide, which contains a recognition sequence for matrix metalloproteinases (MMPs), a class of enzymes often expressed in the tumor microenvironment and inflammatory BBB conditions. Proteolytic cleavage induces PEG release, including the release of four glutamic acid residues, providing a charge switch that triggers a shift of the LNP charge from weakly negative to positive, thus favoring cellular endocytosis and release of siRNA for high silencing efficiency. This work describes the development of this two-stage nanocarrier-system and evaluates the performance in brain endothelial and glioblastoma cells with respect to uptake and gene silencing efficiency. The ability of activation by MMP-triggered dePEGylation and charge shift is demonstrated to substantially increase the uptake and the silencing efficiency of the LNPs.

Twitter Demographics

The data shown below were collected from the profiles of 11 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 100 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 1%
Unknown 99 99%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 21 21%
Student > Master 17 17%
Student > Bachelor 9 9%
Unspecified 6 6%
Student > Doctoral Student 5 5%
Other 14 14%
Unknown 28 28%
Readers by discipline Count As %
Pharmacology, Toxicology and Pharmaceutical Science 14 14%
Medicine and Dentistry 12 12%
Agricultural and Biological Sciences 8 8%
Biochemistry, Genetics and Molecular Biology 7 7%
Unspecified 7 7%
Other 21 21%
Unknown 31 31%

Attention Score in Context

This research output has an Altmetric Attention Score of 10. 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 20 October 2022.
All research outputs
#3,117,636
of 22,986,950 outputs
Outputs from International Journal of Nanomedicine
#184
of 3,837 outputs
Outputs of similar age
#42,702
of 267,288 outputs
Outputs of similar age from International Journal of Nanomedicine
#9
of 153 outputs
Altmetric has tracked 22,986,950 research outputs across all sources so far. Compared to these this one has done well and is in the 86th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,837 research outputs from this source. They receive a mean Attention Score of 4.3. This one has done particularly well, scoring higher than 95% 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 267,288 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 83% of its contemporaries.
We're also able to compare this research output to 153 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 94% of its contemporaries.