Biomedical Engineering Reference
In-Depth Information
issue [15], which has to be tested and investigated before applying the sam-
ples in further studies, in order to exclude effects from aging of samples [16].
2.3 Relations between Nanoparticle
Characteristics and Toxicity
For a given amount of granular matter, the number of particles increases
with decreasing particle size; additionally, finer granularity changes the
material properties. Smaller particles tend to show enhanced diffusivity,
permeation propensity, reactivity, and solubility. These observations raise
concerns that nanoscaled material may show unanticipated
specific
toxicity
(i.e., toxicity per mass), in comparison to microscaled particles.
2.3.1 Possible Origins of Nanoparticle-Specific Toxicity
There are various possible origins of enhanced nanoparticle toxicity, which will
be discussed in the following. Nanoparticles show higher motility and higher-
frequency Brownian motion, which lead to enhanced diffusivity and reduced
sedimentation. Their nanometric size can increase permeation and lead to effec-
tive dissemination and thus enable nanoparticles to reach new sites of action.
For example, in contrast to larger objects, airborne nanoparticles may reach
alveolar cavities of the lung, may show enhanced vascular permeability via cell
junction passage, and may cross cell membranes via endocytosis.
Also, the reactivity and solubility of nanoscaled matter may be signifi-
cantly enhanced. Accumulation and clearance processes from cells, organs,
or the body will generally be affected by particle size. It is a general geo-
metric feature that with decreasing particle size, the specific surface area
(i.e., surface per mass) becomes larger. This increases the specific number
of incomplete or less-tightly bound surface atoms or molecules, and gives
rise to enhanced surface reactivity. Reactions at the nanoparticle surface can
lead to the formation of functional surface groups with enhanced reactiv-
ity or polar character, and affect immobilization and transport properties.
Both are closely related to clearance, accumulation, and toxic properties. In
addition, increased reactivity may accelerate the dissolution rate of surface
constituents, and enhance the bioavailability of a substance in nanoscale
form. Persistent insoluble nanoparticles, on the other hand, are potentially
toxic if they either exhibit or generate radical surface sites that induce oxida-
tive stress to cells, or they initiate frustrated phagocytosis [8]. Unprecedented
toxic effects may therefore arise if their surface functionality enables toxic
nanoparticles to reach new sites of action, for example, the cytoplasm or the
cell nucleus. In this respect, receptor-mediated phagocytosis of functional-
ized nanoparticles emerge as a critical scenario.
