Biomedical Engineering Reference
In-Depth Information
of the caspase-3, -9, and Bcl-2 family genes and their proteins varied with the doses of TiO
2
NPs.
Nanoparticles can interact readily with biomolecules either on the surface or within the cells because
of the small sizes of the nanoparticles. Cellular and subcellular distributions of the particles have
great influences on protein aggregation, gene expression, and cell cytotoxicity (Chen and Gerion
2004; Jiang et al. 2008).
Oxidative stress is known to induce cellular death by apoptosis or necrosis (Hockenbery et al. 1993).
The significant production of ROS and malondialdehyde (MDA) occurred in the mouse spleen treated
with various doses of TiO
2
NPs, indicating that these TiO
2
NP-treated mouse spleens underwent severe
oxidative stress. It has been reported that TiO
2
NPs could be phagocytized by neurons and microglia,
which then released ROS and cause apoptosis (Dunford et al. 1995; Long et al. 2006, 2007; Wang et al.
2008). Interaction between H
2
O
2
and O
2
•− can create •OH and 1O
2
, which are far more destructive and
can peroxidate the unsaturated lipids of the cell membrane (Fridovich 1978; Li et al. 2010).
14.4.3.5 Toxicity of Carbon Nanotubes
Many
in vivo
studies have shown that CNTs delivered to specific areas of the body are not confined
to that area (Deng et al. 2007). For example, intravenously injected CNTs were shown to be taken
up both by the liver and the spleen and then excreted rapidly through the kidneys (Deng et al. 2007;
Schipper et al. 2008). In contrast, SWCNTs injected into the bloodstream of mice persisted within
liver and spleen macrophages (Kupffer cells) (Yang et al. 2008). Inhaled MWCNTs were also shown
to be able to suppress the immune function of the spleen through the signals coming from the lungs
of exposed mice (Mitchell et al. 2007, 2009).
Xiaoyong et al. carried out a study to establish the splenic toxicity of water-soluble MWCNTs
(SMWCNTs) in mice (Xiaoyong et al. 2009). CNTs
in vivo
can be readily scavenged from the blood
and mainly entrapped by the liver, spleen, and lungs. SMWCNTs were used as a model to investi-
gate the possible toxicity of CNTs to mouse spleens. When CNTs were injected into the blood, they
could be quickly scavenged by the RES and the majority accumulated in mouse liver and spleen for
a long time without being metabolized (Wang et al. 2004; Deng et al. 2007, 2008; Yang et al. 2007;
Liu et al. 2008), which might affect the normal function of these tissues.
There may be two ways that the spleen scavenges SMWCNTs from blood circulation. One way
is through opsonization, which makes them easily detectable and eliminated by macrophages in
the spleen (Owens and Peppas 2006). The other way is that SMWCNTs can be trapped by splenic
filtration. The size and deformability of foreign particles play a critical role in their clearance by the
sinusoidal spleens of mice. Particles must be either small or deformable enough to avoid the splenic
filtration process at the inter-endothelial cell slits in the walls of venous sinuses. The slit size rarely
exceeds 200-500 nm in width and thus particles larger than 200 nm probably can be filtered by the
spleen (Moghimi et al. 2001). Since SMWCNTs have dimensions of 270 nm in length and 13 nm in
diameter, the single SMWCNT is hard to be trapped by splenic filtration; however, the aggregated
SMWCNTs can be captured via this mechanism.
Many SMWCNTs accumulate in the spleen and no obvious decrease is observed over 2 months.
It is interesting to note that accumulated SMWCNTs gradually transfer from the red pulp to the
white pulp with increasing exposure times. The spleen is an exclusive immune organ, joining in the
innate and adaptive immune systems. It is organized as a “tree” of branching arterial vessels, in
which the small arterioles end in a venous sinusoidal system where the blood is collected from cords
in the red pulp and transported to vena lienalis. The wall structure of sinuses allows the removal
of foreign particles from circulation by macrophages and monocytes. Thus, it is easy to understand
that SMWCNTs are enriched in the sinuses of red pulp early-on in post exposure. However, white
pulp is organized as lymphoid sheaths with T- and B-cell compartments in the region of the branch-
ing arterial vessels, and is the center of the adaptive immune system (Mebius and Kraal 2005). How
SMWCNTs transfer to the white pulp is currently unclear, but it may come from the translocation of
antigen-presenting cells. The increasing SMWCNTs accumulated in the white pulp probably initi-
ate the adaptive immune response to SMWCNTs (Xiaoyong et al. 2009).
