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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Beilstein+J+Nanotechnol
2016 ; 7
(ä): 1296-1311
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On the pathway of cellular uptake: new insight into the interaction between the
cell membrane and very small nanoparticles
#MMPMID27826504
Messerschmidt C
; Hofmann D
; Kroeger A
; Landfester K
; Mailänder V
; Lieberwirth I
Beilstein J Nanotechnol
2016[]; 7
(ä): 1296-1311
PMID27826504
show ga
For any living cell the exchange with its environment is vital. Therefore, many
different kinds of cargo are able to enter cells via energy-dependent or
-independent routes. Nanoparticles are no exemption. It is known that small
silica nanoparticles with a diameter below 50 nm are taken up by cells and that
their uptake exerts pronounced toxic effects beyond a certain concentration
threshold. However, neither the exact uptake mechanism of these particles nor the
actual reason for their toxicity has yet been elucidated. In this study we
examined the uptake of silica nanoparticles with a diameter of 7, 12 and 22 nm by
means of transmission electron microscopy, accompanied by toxicological assays.
We show that for every particle diameter tested a different membrane morphology
during uptake can be observed and that the amount of particles entering in one
event is different for the three sizes. Silica particles with a diameter of 22 nm
show single-particle internalization with a membrane wrapped around the particles
in the cytosol, whereas 12 nm particles display row-like multi-particle uptake
into elongated membrane structures and those with a diameter of 7 nm or less end
up in tubular endocytic structures containing many particles. These membrane
morphologies proved to be highly reproducible as we found them in five different
cell lines. Additionally, we performed ATP and LDH assays to determine particle
toxicity. Exceeding a certain concentration threshold the nanoparticles showed a
high toxic potential both in the biochemical assay measurements and from
morphological findings. We could not find any hint at the induction of apoptosis,
neither morphologically nor biochemically. In this regard we discuss membrane
damage and consumption as one possible mechanism of toxicity, linking
morphological observations to toxicological findings to bridge the gap in
understanding the mechanism of toxicity of small nanoparticles.