Biomedical Engineering Reference
In-Depth Information
coating (e.g., polyelectrolyte brushes) introduced to maintain colloidal sta-
bility of nanoparticle solutions.
73
Positively charged nanoparticles can easily
interact with negatively charged lipid bilayer cell membranes. Similarly to
cationic polyelectrolytes, interaction of cationic nanoparticles with the cell
membrane causes thinning, disruption of or hole formation in the cell
membrane.
74
For instance, when 3T3 fibroblasts were incubated with gold
nanoparticles (10-15 nm in size) carrying either negatively charged phos-
phonate (-PO(OH)
2
) or positively charged trimethylammonium (-N(CH
3
)
3
)
groups as blocks on the amphiphilic diblock copolymer chains, the cytotoxic
effects were observed at concentrations above 20 nM for the anionic particles
and above 5 nM for the cationic gold nanoparticles and were attributed to
the higher cellular uptake of the cationic particles rather than to the con-
centration of the nanoparticles to which cells were exposed.
73
The cationic
PDDA-coated Ag nanoparticles with the average size of 5 nm were reported to
be the most toxic to mouse macrophage and lung epithelial cells compared
to the uncoated Ag nanoparticles.
75
The use of positively charged surfactants
such as hexadecyltrimethylammonium bromide (CTAB) used for colloidal
stabilization of nanoparticles may also lead to cytotoxicity.
72
On the other
hand, the inorganic nanoparticle cores may induce cytotoxicity by releasing
toxic ions.
76,77
For example, the leaching of silver ions from 25-nm silver
nanoparticles in the presence of algae due to H
2
O
2
production caused
cytotoxic effects to Chlamydomonas reinhardtii.
78
In the case of soluble and
insoluble metal oxides, the exposure of cells to nanoparticles of zinc oxide
resulted in death of all mesothelioma MSTO-211H human or rodent 3T3
fibroblast cells at nanoparticle concentrations above 15 ppm and led to a fast
drop in cell functionality at concentrations as low as 3.75 ppm.
79
The toxic
effect was attributed to the release of Zn
21
ions. However, the cytotoxic effect
of free ions was cell type sensitive. Thus, for example, human MSTO cells were
highly sensitive to Fe
2
O
3
while rodent 3T3 cells were not greatly affected and
remained viable. The toxicity in this case was from the catalytic production of
free radicals through Fenton- and Haber-Weiss-type reactions. Unlike soluble
metal oxides, insoluble oxides including SiO
2
and TiO
2
were found to be not
exceedingly toxic up to 30 ppm.
79
The cytotoxicity of nanoparticles is generally
increased with the particle size decrease that is attributed mainly to increased
reactive surface area for smaller nanoparticles.
80
The cytotoxicity of carbon
nanotubes has been a contradictory issue in the literature
81
and has been
reported to be dependent on a variety of factors such as impurities
82,83
and
surface functionalization.
84
Carbon nanotubes may induce cytotoxic effects to
living cells mainly by physical membrane damage and/or by oxidative stress
through generation of reactive oxygen species.
81
d
n
8
y
4
n
g
|
8
.
6.3 Cytocompatibility of Cell Functionalization
Approaches
Cell surface functionalization can be realized through a conformal protective
layer on the cell surfaces using various surface techniques. Natural and
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