Biomedical Engineering Reference
In-Depth Information
9.3
HEALTH EFFECTS BY CATEGORY
9.3.1 h
ealth
e
ffects
of
f
ullereNes
Fullerenes are spherical nanomaterials having a diameter of about 1 nm. They are also termed
C
60
,
buckminsterfullerene
, or
buckyballs
. Structurally, the simplest fullerenes are composed of 60
linked carbon atoms in a stable icosahedron containing 60 vertices and 32 faces, and hence the
name C
60
. The faces are hexagonal (21) and pentagonal (12) in shape. These nanoparticles were first
described by Kroto et al. in 1985 [136].
As reported by Powell and Karanek [137], fullerene nanoparticles are naturally produced during
combustion processes, such as the burning of fuel or fires. Fullerenes can also be produced artificially
and have recently found applications in pharmaceutical drug delivery and cosmetic products [138].
Considering these applications and direct human exposure, it is important to identify and assess the
biocompatibility and magnitude of the deleterious effects of fullerenes. Also important is the fact that
although fullerenes are described as nanoparticles consisting of 60 or more carbon atoms, typically
they are found as larger agglomerates or clusters frequently termed as colloidal fullerenes. In addi-
tion, fullerenes are available in a variety of physical forms, such as fullerene derivatives, based on the
number of carbon atoms, additional molecules attached to the surface, and the process of fullerene
preparation. Thus, identifying the properties of fullerenes that contribute to their toxicity as well as
their mechanism of such toxicity is highly significant. This requires a detailed analysis of the physi-
cochemical properties of a given fullerene along with the toxicological evaluation [139].
Studies suggest several mechanistic pathways that may be involved in the manifestation of toxic
effects of fullerenes. The commonly identified potential mechanisms for fullerene toxicities include
the induction of an inflammatory response, an increase in oxidative stress, as well as toxicities due
to genetic modifications. Several researchers have attempted to determine possible mechanisms of
fullerene toxicity. Data from these studies are frequently speculative, often inconclusive, and occa-
sionally even contradictory.
Nanoparticles as a general class have been shown to produce inflammatory responses, and this
is thought to be a primary mechanism common to the members of this class, including fullerenes
[140-142]. Rouse et al. [143] studied the potential proinflammatory responses of fullerene-amino
acid complexes
in vitro
using human epidermal keratinocyte cells. The authors demonstrated an
increase in the production of proinflammatory mediators like interleukin-8 and tumor necrosis
factor α (TNF-α) upon exposure to fullerene complexes. Harhaji et al. [144] investigated the influ-
ence of fullerenes (C
60
/C
70
) and polyhydroxylated preparations on TNF-α-induced toxicity in the
mouse, L929 fibroblast cell line. The authors demonstrated a synergistic interaction between C
60
/
C
70
and TNF-α in producing the cytotoxic effects in the cells. However, functionalized fullerenes,
that is polyhydroxylated fullerenes appeared to have a protective activity on the TNF-α-mediated
cell death. The main mechanism involved in the toxicity was speculated to be the modulation of
TNF-α-mediated reactive oxygen species (ROS) production. The study highlighted the fact that the
magnitude of observed toxicities due to fullerenes depends on the type of preparation and it is dif-
ficult to generalize the predictability of toxic effects of fullerenes.
In contrast, Roursgaard et al. [145] showed that at lower concentrations in the lungs, fullerols had
anti-inflammatory effects, whereas they showed proinflammatory effects at higher concentrations
[145]. Similarly, Huang et al. [146] demonstrated the anti-inflammatory effects of fullerene deriva-
tives
in vitro
. The authors demonstrated the free radical scavenging effects of fulleropyrrolidine-
xanthine complex in lipopolysaccharide (LPS)-stimulated J774 macrophage-like cells. Fullerenes
were able to reduce LPS-induced nitric oxide and TNF-α production in these cells. Tsao et al. [147]
studied the anti-inflammatory effects of carboxyfullerene (up to 40 mg/kg) in protection against
Escherichia coli
-mediated meningitis in mice after intraperitoneal injection. The authors suggested
that carboxyfullerene was able to cross the blood-brain barrier and was found to be more effective
in attenuating
E. coli
-induced meningitis compared with dexamethasone.
