Biomedical Engineering Reference
In-Depth Information
The unique, physicochemical properties of NMs may play a vital role in any possible toxic effects
as compared to bulk materials. The size, surface area, composition, and shape are thought to be a
few origins of NM toxicity (Aillon et al. 2009, Lanone and Boczkowski 2006). The particle's size
influences the distribution and elimination of NMs from the body. Size can also modify the intra-
cellular fate of NMs by manipulating the modes of endocytosis, cellular uptake, and the efficiency
of the particle's processing in the endocytic pathway (Lanone and Boczkowski 2006, Rejman et al.
2004).
In vivo
studies of TiO
2
NPs demonstrated that smaller particles (20 nm) led to a persistent
inflammatory response as compared to larger particles (250 nm) in rat lungs (Buzea et al. 2007,
Oberdorster et al. 1994, 2005). The particles in the nanosized range have an exponentially high sur-
face area to volume ratio and are, hence, more reactive to their surrounding biological environment.
Most of the biological interactions of NMs take place on their surfaces. As the size decreases, the
surface area drastically increases, which, in turn, leads to greater proportions of the particle's com-
ponents being exposed. The small size makes it easy for NMs to translocate into organs. It can also
lead to the production of reactive oxygen species (ROS), a contributor of DNA damage (Grabinski
et al. 2007, Shvedova et al. 2004). Further, the surface charge determines the kinetics of the NPs
within the environment in which they are subjected. The charge that the NMs carry on their surface
determines their interactions within the cells. For example, cationic (positively charged) NMs are
considered more toxic as compared to anionic (negatively charged) NMs (Goodman et al. 2004).
Negatively charged moieties on cell membranes (phospholipid heads and other proteins) have a
greater affinity toward disruption by NMs, leading to the cell penetration of these particles.
The presence of several functional groups, which can be controlled by rational design, may
also contribute to cytotoxicity as well as reduce systemic toxicity. Surface coatings on NMs have
been exploited for drug delivery into targeted regions. For example, NPs with a glutathione coating
have been used to deliver paclitaxel into the brain to target brain cancers (Geldenhuys et al. 2011).
Glutathione on the coating interacts with their specific receptors in the brain through which they
permeate the blood-brain barrier. They also demonstrated the reduced toxicity of FDA-approved
PEG-poly(lactic-co-glycolic) acid (PLGA) coatings on NMs.
The chemical composition of NMs, especially at the surface, can modify their interaction with
the body. NMs have been made for prolonged circulation by modifying their surface with chemical
functional groups for targeted drug deliveries. This functionalization of NMs can potentially alter
their interaction with biological components. Such functionalization can also modify the degrada-
tion of some transition metals (e.g., QDs), which may otherwise result in the release of toxins and
free radicals in the body, leading to subsequent cell death. Both nondegradable and biodegradable
NMs can cause detrimental effects to cells through their intracellular accumulation and unexpected
toxic degradants, respectively (Aillon et al. 2009, Garnett and Kallinteri 2006).
Shape is another important factor to be considered when studying nanotoxicity. Shapes that
are spherical have lower aspect ratios, whereas shapes such as spirals and rods have higher aspect
ratios (the ratio between the length and the width of an object). The shape plays a critical role in
the effective clearance by altering interactions with macrophages. The internalization of NMs by
macrophages was found to be modified by altering the actin-driven interactions in macrophages.
The less internalization with rod-like materials relative to spherical materials was evident of pos-
sible shape-based phagocytosis of NMs in alveolar macrophages (Aillon et al. 2009, Champion and
Mitragotri 2006). Similar kinds of results may be yielded by other tissues as well.
NMs with high aspect ratios are more prone to eliciting toxic effects as compared to the ones
with low aspect ratios (Lippmann 1990, Poland et al. 2008). Rod- or spiral-shaped NMs, therefore,
have a greater contact area with cell membranes, leading to partial endocytosis by macrophages, as
the pseudopodium formed to engulf the NMs is unable to enclose them (Hoet et al. 2004) (Figure
1.5a). This damages the macrophages and also causes their hydrolases, cytokines, and oxidants to
be released into the extracellular fluids, leading to further damage. Similarly, high aspect ratios have
been shown to modify macrophages and the reticuloendothelial system (RES) uptake of fibrous
asbestos in the lungs of rats. As a consequence, the longevity in biological systems of these long
