Page 226 - Environmental Nanotechnology Applications and Impacts of Nanomaterials

Principles and Procedures to Assess Nanomaterial Toxicity 211

of the mitochondrial membrane potential, increased ROS production,
and the induction of programmed cell death [30, 32, 35]. The basis for
the mitochondrial response may be direct oxidant injury by free radi-
cals, as well as the effect of free ionized calcium, which acts as an intra-
cellular pathway by which oxidative stress can indirectly impact
mitochondrial function. Research on ambient UFP also reveals the inter-
esting possibility that the mitochondrion could be directly targeted by
nanoparticles [19, 21, 36]. Ambient UFP lodge in the damaged mito-
chondria of exposed macrophages and epithelial cells [19, 21, 37]. Other
nano-sized materials have been demonstrated to target mitochondria.
As early as 1970, de Lorenzo found that colloidal gold particles (50 nm)
delivered intra-nasally in the squirrel monkey cross the olfactory
nerve/mitral cell synapse and have the capability to lodge in mitochon-
(CO H) , has been
dria of the mitral cells [38]. A fullerene derivative, C 61 2 2
shown capable of crossing the surface membrane with preferential
localization in mitochondria [39]. The same observation was made
with block copolymers, which are water-soluble biocompatible nano-
containers that can be used for drug delivery. Fluorescent-labeled block
copolymer micelles localize in a variety of cytoplasmic organelles, includ-
ing mitochondria [40]. In summary, mitochondrial targeting and damage
could constitute an important mechanism of NM toxicity. Changes in

mitochondrial membrane potential, calcium uptake, O production, car-
2
diolipin integrity, and induction of cellular apoptosis represent testable
responses.

Need for standardized materials
Well-characterized NM that have undergone rigorous biological testing
to show reproducible biological effects are required as standard refer-
ence materials to compare the effects of newly introduced NM. These
benchmark materials will help to prevent the discrepancy and para-
doxical findings that arise from the study of NM types in different
hands. The choice of such standards should be based on the physico-
chemical properties of the material, frequency of use, volume of pro-
duction, and likelihood of release as a singlet substance to which humans
and the environment may be exposed. Carbon black is a bulk-
manufactured material that is in widespread use, including as a powder
that can be inhaled. In a highly purified form, carbon black is incapable
of ROS generation and devoid of cytotoxicity [41]. In their unadulterated
form these could serve as a benchmark material that does not engage
in ROS production and oxidant injury. TiO nanoparticles, also widely
2
used and bulk-produced, can be considered as a representative material
capable of ROS production under abiotic conditions [41]. Carbon nan-
otubes could be used as a NM that, due to their large aspect ratios,