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Tumour-specific delivery of siRNA-coupled superparamagnetic iron oxide nanoparticles, targeted against PLK1, stops progression of pancreatic cancer

Overview of attention for article published in Gut, May 2016
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Title
Tumour-specific delivery of siRNA-coupled superparamagnetic iron oxide nanoparticles, targeted against PLK1, stops progression of pancreatic cancer
Published in
Gut, May 2016
DOI 10.1136/gutjnl-2016-311393
Pubmed ID
Authors

Ujjwal M Mahajan, Steffen Teller, Matthias Sendler, Raghavendra Palankar, Cindy van den Brandt, Theresa Schwaiger, Jens-Peter Kühn, Silvia Ribback, Gunnar Glöckl, Matthias Evert, Werner Weitschies, Norbert Hosten, Frank Dombrowski, Mihaela Delcea, Frank-Ulrich Weiss, Markus M Lerch, Julia Mayerle

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies and is projected to be the second leading cause of cancer-related death by 2030. Despite extensive knowledge and insights into biological properties and genetic aberrations of PDAC, therapeutic options remain temporary and ineffective. One plausible explanation for the futile response to therapy is an insufficient and non-specific delivery of anticancer drugs to the tumour site. Superparamagnetic iron oxide nanoparticles (SPIONs) coupled with siRNA directed against the cell cycle-specific serine-threonine-kinase, Polo-like kinase-1 (siPLK1-StAv-SPIONs), could serve a dual purpose for delivery of siPLK1 to the tumour and for non-invasive assessment of efficiency of delivery in vivo by imaging the tumour response. siPLK1-StAv-SPIONs were designed and synthesised as theranostics to function via a membrane translocation peptide with added advantage of driving endosomal escape for mediating transportation to the cytoplasm (myristoylated polyarginine peptides) as well as a tumour-selective peptide (EPPT1) to increase intracellular delivery and tumour specificity, respectively. A syngeneic orthotopic as well as an endogenous cancer model was treated biweekly with siPLK1-StAv-SPIONs and tumour growth was monitored by small animal MRI. In vitro and in vivo experiments using a syngeneic orthotopic PDAC model as well as the endogenous LSL-Kras(G12D), LSL-Trp53(R172H), Pdx-1-Cre model revealed significant accumulation of siPLK1-StAv-SPIONs in PDAC, resulting in efficient PLK1 silencing. Tumour-specific silencing of PLK1 halted tumour growth, marked by a decrease in tumour cell proliferation and an increase in apoptosis. Our data suggest siPLK1-StAv-SPIONs with dual specificity residues for tumour targeting and membrane translocation to represent an exciting opportunity for targeted therapy in patients with PDAC.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 89 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Germany 1 1%
Unknown 88 99%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 14 16%
Researcher 14 16%
Student > Bachelor 13 15%
Student > Master 8 9%
Other 5 6%
Other 11 12%
Unknown 24 27%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 13 15%
Medicine and Dentistry 11 12%
Pharmacology, Toxicology and Pharmaceutical Science 9 10%
Agricultural and Biological Sciences 8 9%
Engineering 4 4%
Other 16 18%
Unknown 28 31%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. 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 01 November 2016.
All research outputs
#14,715,070
of 25,559,053 outputs
Outputs from Gut
#5,558
of 7,400 outputs
Outputs of similar age
#159,933
of 326,593 outputs
Outputs of similar age from Gut
#36
of 64 outputs
Altmetric has tracked 25,559,053 research outputs across all sources so far. This one is in the 41st percentile – i.e., 41% of other outputs scored the same or lower than it.
So far Altmetric has tracked 7,400 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 19.9. This one is in the 24th percentile – i.e., 24% of its peers scored the same or lower than it.
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 326,593 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 50% of its contemporaries.
We're also able to compare this research output to 64 others from the same source and published within six weeks on either side of this one. This one is in the 45th percentile – i.e., 45% of its contemporaries scored the same or lower than it.