Quantitative bioimage analytics enables measurement of targeted cellular stress response induced by celastrol-loaded nanoparticles

A1 Journal article (refereed)


Internal Authors/Editors


Publication Details

List of Authors: Niemelä E, Desai D, Lundsten E, Rosenholm JM, Kankaanpää P, Eriksson JE
Publisher: Springer Netherlands
Publication year: 2019
Journal: Cell Stress and Chaperones
Volume number: 24
Issue number: 4
Start page: 735
End page: 748
ISSN: 1355-8145
eISSN: 1466-1268


Abstract

The cellular stress response, which provides protection against
proteotoxic stresses, is characterized by the activation of heat shock
factor 1 and the formation of nuclear stress bodies (nSBs). In this
study, we developed a computerized method to quantify the formation and
size distribution of nSBs, as stress response induction is of interest
in cancer research, neurodegenerative diseases, and in other
pathophysiological processes. We employed an advanced bioimaging and
analytics workflow to enable quantitative detailed subcellular analysis
of cell populations even down to single-cell level. This type of
detailed analysis requires automated single cell analysis to allow for
detection of both size and distribution of nSBs. For specific induction
of nSB we used mesoporous silica nanoparticles (MSNs) loaded with
celastrol, a plant-derived triterpene with the ability to activate the
stress response. To enable specific targeting, we employed folic acid
functionalized nanoparticles, which yields targeting to folate receptor
expressing cancer cells. In this way, we could assess the ability to
quantitatively detect directed and spatio-temporal nSB induction using
2D and 3D confocal imaging. Our results demonstrate successful
implementation of an imaging and analytics workflow based on a freely
available, general-purpose software platform, BioImageXD, also
compatible with other imaging modalities due to full 3D/4D and
high-throughput batch processing support. The developed quantitative
imaging analytics workflow opens possibilities for detailed stress
response examination in cell populations, with significant potential in
the analysis of targeted drug delivery systems related to cell stress
and other cytoprotective cellular processes.


Documents


Last updated on 2020-21-02 at 03:53