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Mechanistic studies of Gemcitabine-loaded nanoplatforms in resistant pancreatic cancer cells

Overview of attention for article published in BMC Cancer, September 2012
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Title
Mechanistic studies of Gemcitabine-loaded nanoplatforms in resistant pancreatic cancer cells
Published in
BMC Cancer, September 2012
DOI 10.1186/1471-2407-12-419
Pubmed ID
Authors

Anne-Laure Papa, Sudipta Basu, Poulomi Sengupta, Deboshri Banerjee, Shiladitya Sengupta, Rania Harfouche

Abstract

Pancreatic cancer remains the deadliest of all cancers, with a mortality rate of 91%. Gemcitabine is considered the gold chemotherapeutic standard, but only marginally improves life-span due to its chemical instability and low cell penetrance. A new paradigm to improve Gemcitabine's therapeutic index is to administer it in nanoparticles, which favour its delivery to cells when under 500 nm in diameter. Although promising, this approach still suffers from major limitations, as the choice of nanovector used as well as its effects on Gemcitabine intracellular trafficking inside pancreatic cancer cells remain unknown. A proper elucidation of these mechanisms would allow for the elaboration of better strategies to engineer more potent Gemcitabine nanotherapeutics against pancreatic cancer. Gemcitabine was encapsulated in two types of commonly used nanovectors, namely poly(lactic-co-glycolic acid) (PLGA) and cholesterol-based liposomes, and their physico-chemical parameters assessed in vitro. Their mechanisms of action in human pancreatic cells were compared with those of the free drug, and with each others, using cytotoxity, apoptosis and ultrastructural analyses. Physico-chemical analyses of both drugs showed high loading efficiencies and sizes of less than 200 nm, as assessed by dynamic light scattering (DLS) and transmission electron microscopy (TEM), with a drug release profile of at least one week. These profiles translated to significant cytotoxicity and apoptosis, as well as distinct intracellular trafficking mechanisms, which were most pronounced in the case of PLGem showing significant mitochondrial, cytosolic and endoplasmic reticulum stresses. Our study demonstrates how the choice of nanovector affects the mechanisms of drug action and is a crucial determinant of Gemcitabine intracellular trafficking and potency in pancreatic cancer settings.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 55 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 55 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 11 20%
Researcher 8 15%
Student > Master 8 15%
Student > Bachelor 7 13%
Student > Doctoral Student 6 11%
Other 5 9%
Unknown 10 18%
Readers by discipline Count As %
Pharmacology, Toxicology and Pharmaceutical Science 10 18%
Agricultural and Biological Sciences 7 13%
Chemistry 6 11%
Engineering 5 9%
Materials Science 4 7%
Other 9 16%
Unknown 14 25%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 24 September 2012.
All research outputs
#14,733,275
of 22,678,224 outputs
Outputs from BMC Cancer
#3,659
of 8,245 outputs
Outputs of similar age
#103,757
of 170,921 outputs
Outputs of similar age from BMC Cancer
#50
of 95 outputs
Altmetric has tracked 22,678,224 research outputs across all sources so far. This one is in the 32nd percentile – i.e., 32% of other outputs scored the same or lower than it.
So far Altmetric has tracked 8,245 research outputs from this source. They receive a mean Attention Score of 4.3. This one has gotten more attention than average, scoring higher than 50% 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 170,921 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 37th percentile – i.e., 37% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 95 others from the same source and published within six weeks on either side of this one. This one is in the 42nd percentile – i.e., 42% of its contemporaries scored the same or lower than it.