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Enhanced cellular uptake and long-term retention of chitosan-modified iron-oxide nanoparticles for MRI-based cell tracking

Overview of attention for article published in International Journal of Nanomedicine, August 2012
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Title
Enhanced cellular uptake and long-term retention of chitosan-modified iron-oxide nanoparticles for MRI-based cell tracking
Published in
International Journal of Nanomedicine, August 2012
DOI 10.2147/ijn.s28294
Pubmed ID
Authors

Sasha H Bakhru, Eda Altiok, Christopher Highley, Daniel Delubac, Joseph Suhan, T Kevin Hitchens, Chien Ho, Stefan Zappe

Abstract

Tracking cells after therapeutic transplantation is imperative for evaluation of implanted cell fate and function. In this study, ultrasmall superparamagnetic iron oxide nanoparticles (USPIO NPs) were surface functionalized with water-soluble chitosan, a cationic polysaccharide that mediates enhanced endocytic uptake, endosomal escape into the cytosol, and subsequent long-term retention of nanoparticles. NP surface and chitosan were independently fluorescently labeled. Our NPs enable NP trafficking studies and determination of fate beyond uptake by fluorescence microscopy as well as tracking of labeled cells as localized regions of hypointensity in T(2)*-weighted magnetic resonance imaging (MRI) images. Adult rat neural stem cells (NSCs) were labeled with NPs, and assessment of NSC proliferation rates and differentiation potential revealed no significant differences between labeled and unlabeled NSCs. Significantly enhanced uptake of chitosan NPs in comparison to native NPs was confirmed by transmission electron microscopy, nuclear magnetic resonance (NMR) spectroscopy and in vitro cellular MRI at 11.7 Tesla. While only negligible fractions of native NPs enter cells, chitosan NPs appear within membranous vesicles within 2 hours of exposure. Additionally, chitosan-functionalized NPs escaped from membrane-bound vesicles within days, circumventing NP endo-lysosomal trafficking and exocytosis and hence enabling long-term tracking of labeled cells. Finally, our labeling strategy does not contain any NSC-specific reagents. To demonstrate general applicability across a variety of primary and immortalized cell types, embryonic mouse NSCs, mouse embryonic stem cells, HEK 293 kidney cells, and HeLa cervical cancer cells were additionally exposed to chitosan-USPIO NPs and exhibited similarly efficient loading as verified by NMR relaxometry. Our efficient and versatile labeling technology can support cell tracking with close to single cell resolution by MRI in vitro, for example, in complex tissue models not optically accessible by confocal or multi-photon fluorescence microscopy, and potentially in vivo, for example, in animal models of human disease or injury.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 65 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 2%
India 1 2%
Saudi Arabia 1 2%
Unknown 62 95%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 15 23%
Researcher 12 18%
Student > Master 10 15%
Student > Bachelor 5 8%
Student > Doctoral Student 5 8%
Other 7 11%
Unknown 11 17%
Readers by discipline Count As %
Agricultural and Biological Sciences 19 29%
Medicine and Dentistry 9 14%
Biochemistry, Genetics and Molecular Biology 7 11%
Chemistry 5 8%
Engineering 3 5%
Other 9 14%
Unknown 13 20%
Attention Score in Context

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 22 August 2012.
All research outputs
#20,823,121
of 25,584,565 outputs
Outputs from International Journal of Nanomedicine
#3,113
of 4,077 outputs
Outputs of similar age
#140,428
of 179,468 outputs
Outputs of similar age from International Journal of Nanomedicine
#66
of 74 outputs
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So far Altmetric has tracked 4,077 research outputs from this source. They receive a mean Attention Score of 4.8. This one is in the 13th percentile – i.e., 13% of its peers scored the same or lower than it.
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