Biomedical Engineering Reference
In-Depth Information
3.5.1 s tructural p ropertIes -d epeNdeNt t oxIcIty
Nanoparticle structural properties are important in understanding their relation to nanotoxic behav-
iors. Structural properties include the various attributes of a nanosystem, such as shape, aspect ratio,
surface morphology, structural arrangement, spatial distribution, density, and geometric features.
Out of these attributes, the key attributes such as shape, aspect ratio, structural arrangement, surface
chemistry, and surface charge, which are responsible for various toxicities (by different mecha-
nisms) are discussed here. The development of electron microscopy improved the accessibility and
feasibility of determining these attributes at the nanometer scale to identify their roles in specific
toxicities.
3.5.1.1 Particle Shape and Aspect Ratio
It was found that the particle aspect ratio is directly proportional to its toxicity. For example, lung
cancer was associated with asbestos fibers (size >10 μm), mesothelioma with fibers (size >5 μm),
and asbestosis with fibers (size >2 μm). All of these fibers had a minimum thickness of about
150 nm (Lippmann 1990). Long fibers (longer than 20 μm for humans) will not be effectively
cleared from the respiratory tract due to the inability of macrophages to phagocytize them (Hoet
et al. 2004). The biopersistence of these long aspect ratio fibers leads to long-term carcinogenic
effects (Oberdörster 2002).
The toxicity of long aspect fibers is closely related to their bio-durability, depending on its disso-
lution and mechanical properties (breaking). Longer fibers that break perpendicularly to their long
axis become shorter and can be removed by macrophages. Asbestos fibers break longitudinally,
resulting in more fibers with smaller diameters, being harder to clear (Hoet et al. 2004). If clear-
ance from the lung is slow, the longer these fibers will stay in the lung, the higher the probability
of an adverse response. Fibers that are sufficiently soluble in lung fluid can disappear in a matter of
months, while insoluble fibers are likely to remain in the lungs indefinitely. Even short, insoluble
fibers that are efficiently phagocytized by alveolar macrophages may induce biochemical reactions
(the release of cytokines, ROS, and other mediators).
Long aspect ratio engineered nanoparticles, such as CNTs, have recently attracted a lot of atten-
tion due to their possible negative health effects (Warheit et al. 2004; Cui et al. 2005; Monteiro-
Riviere et al. 2005; Muller et al. 2005) (Table 3.6), as suggested by their morphological similarities
with asbestos. CNTs can be single-walled (SWCNTs) or multi-walled (MWCNTs), with varying
diameters and lengths and closed capped sections or open ends (Dai 2002). Due to their hydropho-
bicity and tendency to aggregate, they are harmful to living cells in culture (Monteiro-Riviere et al.
2005; Cui et al. 2005). For many applications, CNTs are oxidized to create hydroxyl and carboxyl
groups, especially at their ends, making them more readily dispersed in aqueous solutions (Bottini
et  al. 2006). SWCNTs were reported to produce significant pulmonary toxicity as compared to
spherical particles (amorphous carbon black) (Lam et al. 2004; Bottini et al. 2006). For compari-
son purposes, equal doses of carbon black or silica nanoparticles did not induce granulomas, nor
thickening of the alveolar wall, causing only weak inflammation and limited damage. The enhanced
toxicity was attributed to its physicochemical properties and fibrous nature. CNTs are either not
eliminated from the lungs or are very slowly eliminated; 81% are found in rat lungs 60 days after
exposure (Muller et al. 2005).
3.5.1.2 Structural Arrangement (Crystalline Form)
There is quite a distinction between composition and chemistry. Although particles may have similar
compositions, they may have different chemical or crystalline structures. The toxicity of a material
depends on the type of its crystalline nature (Gurr et al. 2005). For example, rutile and anatase, both
allotropes of titanium dioxide (i.e., polymorphs with the same chemical composition but different
crystalline structure), possess different chemical and physical properties. Table 3.7 shows different
crystalline forms of various types of nanoparticles with their toxicities and the mechanism involved.
Search WWH ::




Custom Search