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Mechanisms of complement activation by dextran-coated superparamagnetic iron oxide (SPIO) nanoworms in mouse versus human serum

Overview of attention for article published in Particle and Fibre Toxicology, November 2014
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Title
Mechanisms of complement activation by dextran-coated superparamagnetic iron oxide (SPIO) nanoworms in mouse versus human serum
Published in
Particle and Fibre Toxicology, November 2014
DOI 10.1186/s12989-014-0064-2
Pubmed ID
Authors

Nirmal K Banda, Gaurav Mehta, Ying Chao, Guankui Wang, Swetha Inturi, Liliane Fossati-Jimack, Marina Botto, LinPing Wu, Seyed Moein Moghimi, Dmitri Simberg

Abstract

BackgroundThe complement system is a key component of innate immunity implicated in the neutralization and clearance of invading pathogens. Dextran coated superparamagnetic iron oxide (SPIO) nanoparticle is a promising magnetic resonance imaging (MRI) contrast agent. However, dextran SPIO has been associated with significant number of complement-related side effects in patients and some agents have been discontinued from clinical use (e.g., Feridex¿). In order to improve the safety of these materials, the mechanisms of complement activation by dextran-coated SPIO and the differences between mice and humans need to be fully understood.Methods20 kDa dextran coated SPIO nanoworms (SPIO NW) were synthesized using Molday precipitation procedure. In vitro measurements of C3 deposition on SPIO NW using sera genetically deficient for various components of the classical pathway (CP), lectin pathway (LP) or alternative pathway (AP) components were used to study mechanisms of mouse complement activation. In vitro measurements of fluid phase markers of complement activation C4d and Bb and the terminal pathway marker SC5b-C9 in normal and genetically deficient sera were used to study the mechanisms of human complement activation. Mouse data were analyzed by non-paired t-test, human data were analyzed by ANOVA followed by multiple comparisons with Student-Newman-Keuls test.ResultsIn mouse sera, SPIO NW triggered the complement activation via the LP, whereas the AP contributes via the amplification loop. No involvement of the CP was observed. In human sera the LP together with the direct enhancement of the AP turnover was responsible for the complement activation. In two samples out of six healthy donors there was also a binding of anti-dextran antibodies and C1q, suggesting activation via the CP, but that did not affect the total level of C3 deposition on the particles.ConclusionsThere were important differences and similarities in the complement activation by SPIO NW in mouse versus human sera. Understanding the mechanisms of immune recognition of nanoparticles in mouse and human systems has important preclinical and clinical implications and could help design more efficient and safe nano-formulations.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 35 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Italy 1 3%
Unknown 34 97%

Demographic breakdown

Readers by professional status Count As %
Researcher 9 26%
Student > Ph. D. Student 7 20%
Student > Master 4 11%
Student > Bachelor 3 9%
Student > Doctoral Student 3 9%
Other 4 11%
Unknown 5 14%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 6 17%
Medicine and Dentistry 5 14%
Materials Science 3 9%
Pharmacology, Toxicology and Pharmaceutical Science 3 9%
Agricultural and Biological Sciences 3 9%
Other 9 26%
Unknown 6 17%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 27 November 2014.
All research outputs
#10,020,010
of 12,521,989 outputs
Outputs from Particle and Fibre Toxicology
#270
of 370 outputs
Outputs of similar age
#192,262
of 286,821 outputs
Outputs of similar age from Particle and Fibre Toxicology
#26
of 33 outputs
Altmetric has tracked 12,521,989 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 370 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.7. This one is in the 22nd percentile – i.e., 22% 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 286,821 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 18th percentile – i.e., 18% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 33 others from the same source and published within six weeks on either side of this one. This one is in the 27th percentile – i.e., 27% of its contemporaries scored the same or lower than it.