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Effective siRNA delivery to inflamed primary vascular endothelial cells by anti-E-selectin and anti-VCAM-1 PEGylated SAINT-based lipoplexes

Overview of attention for article published in International Journal of Pharmaceutics, November 2013
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  • Good Attention Score compared to outputs of the same age (67th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (64th percentile)

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Title
Effective siRNA delivery to inflamed primary vascular endothelial cells by anti-E-selectin and anti-VCAM-1 PEGylated SAINT-based lipoplexes
Published in
International Journal of Pharmaceutics, November 2013
DOI 10.1016/j.ijpharm.2013.11.008
Pubmed ID
Authors

Niek G.J. Leus, Eduard G. Talman, Pranov Ramana, Piotr S. Kowalski, Titia E. Woudenberg-Vrenken, Marcel H.J. Ruiters, Grietje Molema, Jan A.A.M. Kamps

Abstract

The endothelium represents an attractive therapeutic target due to its pivotal role in many diseases including chronic inflammation and cancer. Small interfering RNAs (siRNAs) specifically interfere with the expression of target genes and are considered an important new class of therapeutics. However, due to their size and charge, siRNAs do not spontaneously enter unperturbed endothelial cells (EC). To overcome this problem, we developed novel lipoplexes for siRNA delivery that are based on the cationic amphiphilic lipid SAINT-C18. Antibodies recognizing disease induced cell adhesion molecules were employed to create cell specificity resulting in so-called antibody-SAINTargs. To improve particle stability, antibody-SAINTargs were further optimized for EC-specific siRNA-mediated gene silencing by addition of polyethylene glycol (PEG). Although PEGylated antibody-SAINTargs maintained specificity, they lost their siRNA delivery capacity. Coupling of antibodies to the distal end of PEG (so-called antibody-SAINTPEGargs), resulted in anti-E-selectin- and anti-vascular cell adhesion molecule (VCAM)-1-SAINTPEGarg that preserved their antigen recognition and their capability to specifically deliver siRNA into inflammation-activated primary endothelial cells. The enhanced uptake of siRNA by antibody-SAINTPEGargs was followed by improved silencing of the target gene VE-cadherin, demonstrating that antibody-SAINTPEGargs were capable of functionally delivering siRNA into primary endothelial cells originating from different vascular beds. In conclusion, the newly developed, physicochemically stable, and EC-specific siRNA carrying antibody-SAINTPEGargs selectively down-regulate target genes in primary endothelial cells that are generally difficult to transfect.

X Demographics

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The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 25 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Russia 1 4%
Unknown 24 96%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 5 20%
Student > Master 5 20%
Professor 3 12%
Researcher 3 12%
Student > Postgraduate 2 8%
Other 3 12%
Unknown 4 16%
Readers by discipline Count As %
Agricultural and Biological Sciences 5 20%
Pharmacology, Toxicology and Pharmaceutical Science 4 16%
Biochemistry, Genetics and Molecular Biology 4 16%
Medicine and Dentistry 3 12%
Chemistry 2 8%
Other 2 8%
Unknown 5 20%
Attention Score in Context

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 22 March 2022.
All research outputs
#7,959,659
of 25,371,288 outputs
Outputs from International Journal of Pharmaceutics
#2,405
of 8,178 outputs
Outputs of similar age
#68,676
of 224,654 outputs
Outputs of similar age from International Journal of Pharmaceutics
#23
of 65 outputs
Altmetric has tracked 25,371,288 research outputs across all sources so far. This one has received more attention than most of these and is in the 67th percentile.
So far Altmetric has tracked 8,178 research outputs from this source. They receive a mean Attention Score of 4.4. This one has gotten more attention than average, scoring higher than 69% 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 224,654 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 65 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 64% of its contemporaries.