Biomedical Engineering Reference
In-Depth Information
to humans, such as the injection of smart drug-delivery systems and the application of cosmetics to
the skin and diagnostic markers. In a few cases, there could be an unintended uptake, an example of
which could be the ingestion of NPs used in food-packaging technology (Paul et al. 2006).
13.1.2 N
aNoMaterIal
t
oxIcIty
: t
he
u
NderlyINg
f
actors
Nanomaterials have unique properties and characteristics relative to bulk materials (e.g., high
surface-area-to-volume ratio) that may endow them with unique mechanisms of toxicity from xeno-
biotics. Particularly, toxicity has been thought to originate from nanomaterial size and surface area,
shape, and composition as reviewed by Lanone et al. (2006). The three features—size, surface, and
shape—discussed below, either independently or in combination, may ultimately be shown in the
future to predict the toxicity of NPs.
13.1.2.1 Size
Owing to their small size, NPs can cross cell membranes and penetrate blood vessel walls and the
blood-brain barrier via passive and active diffusion, eventually interfering with cellular functions
(Geiser et al. 2005).
13.1.2.2 Surface
For the same mass of any particular material, the combined surface area of a particle is inversely
proportional to particle size. If the toxic properties of particles are determined by interactions
occurring at the interface between particles and biological systems, toxic responses should correlate
with the total surface area of particles. In fact, it was observed in animal studies that the inflamma-
tory response to inhaled TiO
2
particulates of different sizes, including the nanoscale range, varied
as a function of the surface area (Oberdorster 2000).
13.1.2.3 Shape
One of the benefits of nanotechnology is the ability to control the material structure with atomic
precision. This control of materials on a nanoscale results in our ability to generate an immense
number of engineered NPs with different shapes. Examples of the simplest engineered NPs are
spheres, tubes, wires, rods, belts, and flakes. Examples of more complex engineered NPs are tri-
pods, flowers, and brushes. Finally, the most complex NPs are three-dimensional structures such
as multifunctional nanoscale particles, for example, functionalized liposomes, virosomes, and den-
drimers (Oberdorster 2000).
13.1.3 e
xposure
aNd
d
ose
M
etrIcs
Historically, a mass-based paradigm has been employed by industrial hygienists to assess worker
exposures to airborne particulates. The exposure and dose metrics for engineered NPs in the work-
place are now actively under investigation because NPs have such little mass to measure. Since
NPs have little mass, a new exposure and dose metrics may be needed. Currently, particle number
and particle surface area are being studied as an exposure and dose metric. An exposure and dose
metric for engineered nanoscale materials, which have a range of structures, chemical composi-
tions, or both, will depend on the mechanism of their toxicological and pharmacokinetic behavior
(Nel et al. 2006). For example, poorly soluble, low-toxicity particles, which interact with biological
systems at the particle surface, can have their exposure and dose expressed as a combined surface
area. Consequently, experimental studies in rodents and cell cultures have shown that the toxicity
of nanoscale particles is greater than that of the same mass of larger particles of a similar surface
area; chemical composition correlates best with the observed toxicological responses (Oberdörster
et al. 1994; Tran et al. 2000).
