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The use of collagen-based scaffolds to simulate prostate cancer bone metastases with potential for evaluating delivery of nanoparticulate gene therapeutics

Overview of attention for article published in Clinical Materials, July 2015
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Title
The use of collagen-based scaffolds to simulate prostate cancer bone metastases with potential for evaluating delivery of nanoparticulate gene therapeutics
Published in
Clinical Materials, July 2015
DOI 10.1016/j.biomaterials.2015.07.019
Pubmed ID
Authors

Kathleen A. Fitzgerald, Jianfeng Guo, Erica G. Tierney, Caroline M. Curtin, Meenakshi Malhotra, Raphael Darcy, Fergal J. O'Brien, Caitriona M. O'Driscoll

Abstract

Prostate cancer bone metastases are a leading cause of cancer-related death in men with current treatments offering only marginally improved rates of survival. Advances in the understanding of the genetic basis of prostate cancer provide the opportunity to develop gene-based medicines capable of treating metastatic disease. The aim of this work was to establish a 3D cell culture model of prostate cancer bone metastasis using collagen-based scaffolds, to characterise this model, and to assess the potential of the model to evaluate delivery of gene therapeutics designed to target bone metastases. Two prostate cancer cell lines (PC3 and LNCaP) were cultured in 2D standard culture and compared to 3D cell growth on three different collagen-based scaffolds (collagen and composites of collagen containing either glycosaminoglycan or nanohydroxyapatite). The 3D model was characterised for cell proliferation, viability and for matrix metalloproteinase (MMP) enzyme and Prostate Specific Antigen (PSA) secretion. Chemosensitivity to docetaxel treatment was assessed in 2D in comparison to 3D. Nanoparticles (NPs) containing siRNA formulated using a modified cyclodextrin were delivered to the cells on the scaffolds and gene silencing was quantified. Both prostate cancer cell lines actively infiltrated and proliferated on the scaffolds. Cell culture in 3D resulted in reduced levels of MMP1 and MMP9 secretion in PC3 cells. In contrast, LNCaP cells grown in 3D secreted elevated levels of PSA, particularly on the scaffold composed of collagen and glycosaminoglycans. Both cell lines grown in 3D displayed increased resistance to docetaxel treatment. The cyclodextrin.siRNA nanoparticles achieved cellular uptake and knocked down the endogenous GAPDH gene in the 3D model. In conclusion, development of a novel 3D cell culture model of prostate cancer bone metastasis has been initiated resulting, for the first time, in the successful delivery of gene therapeutics in a 3D in vitro model. Further enhancement of this model will help elucidate the pathogenesis of prostate cancer and also accelerate the design of effective therapies which can penetrate into the bone microenvironment for prostate cancer therapy.

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X Demographics

The data shown below were collected from the profiles of 5 X users 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 169 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Colombia 1 <1%
India 1 <1%
Unknown 167 99%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 36 21%
Researcher 25 15%
Student > Bachelor 25 15%
Student > Master 20 12%
Student > Postgraduate 10 6%
Other 20 12%
Unknown 33 20%
Readers by discipline Count As %
Engineering 28 17%
Agricultural and Biological Sciences 25 15%
Biochemistry, Genetics and Molecular Biology 22 13%
Medicine and Dentistry 17 10%
Materials Science 13 8%
Other 19 11%
Unknown 45 27%
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 11 November 2015.
All research outputs
#14,600,553
of 25,374,647 outputs
Outputs from Clinical Materials
#8,553
of 10,751 outputs
Outputs of similar age
#126,298
of 276,422 outputs
Outputs of similar age from Clinical Materials
#63
of 111 outputs
Altmetric has tracked 25,374,647 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 10,751 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.8. This one is in the 20th percentile – i.e., 20% 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 276,422 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 53% of its contemporaries.
We're also able to compare this research output to 111 others from the same source and published within six weeks on either side of this one. This one is in the 43rd percentile – i.e., 43% of its contemporaries scored the same or lower than it.