Biomedical Engineering Reference
In-Depth Information
DF-1 on a commonly observed phenotype that was apparent within 1 to 2 days after ion-
izing radiation exposure (~40 Gy) of zebrafish. This phenotype is described as “curly-up”
or cup and was ascribed to defects in midline development of zebrafish embryos. Finally,
the study concluded that throughout the dose range tested, DF-1 markedly reduced the
incidence of cup. Depending on the ionizing radiation dose, it either reduced the severity
or abolished the dorsal curvature altogether. It was significant to note that DF-1 did not
cause any adverse effects on normal zebrafish morphology or viability in the concentra-
tion range tested (1-1000 μmol/L). DF-1 (100 μmol/L) was reported to markedly attenuate
overall and organ-specific radiation-induced toxicity when given within 3 h before or up
to 15 min after radiation exposure. However, DF-1 is not capable of protecting within
30 min after ionizing radiation. The degree of DF-1 radioprotection was comparable with
amifostine (4 mmol/L). Moreover, the study evidenced that protection against radiation-
associated toxicity using DF-1 in zebrafish embryos was associated with marked reduc-
tion of radiation-induced ROS. Finally, the authors concluded that DF-1 offered excellent
antioxidant properties against radiation-induced damage. This study has implications in
developing drugs for the military during radiation attacks. Yin et al. [136] reported that
three different types of water-soluble fullerenes materials may intercept all the major
physiologically relevant ROS. They used a carboxyfullerene derivative [C
60
(C(COOH)
2
)
2
]
and a fullerenol derivative [C
60
(OH)
22
] and C
82
-derived gadofullerene. The study demon-
strated that these functionalized fullerenes can protect cells against hydrogen peroxide-
induced oxidative damage, stabilize the mitochondrial membrane potential, and reduce
intracellular ROS production. Furthermore, in vitro studies using human lung adenocar-
cinoma cell line A549 and rat brain capillary endothelial cell line indicated that these
functionalized fullerenes reduces hydrogen peroxide-induced cytotoxicity, free radical
formation, and mitochondrial damage. This result indicates that the gadofullerene deriva-
tive protected against oxidative injury to cellular mitochondria better than the other two
fullerene derivatives [136]. Their study represented the first report that different types of
fullerene derivatives can scavenge all physiologically relevant ROS. The article concluded
that the role of oxidative stress and damage in the etiology and progression of many dis-
eases suggests that these fullerene derivatives may be valuable in vivo cytoprotective and
therapeutic agents.
Functionalized Fullerenes as MRI Contrast Agents
Fullerenes that are capable of encapsulating metal atom inside the fullerene cage are called
endohedral metallofullerenes
, and they represent another class of functionalized fullerenes.
Similar to a liposome, protecting its encapsulated drug, the fullerene cage in a metallo-
fullerene protects the metal inside both against chemical or enzymatic activity within the
body and the unwarranted release of the metal. The ability to design water-soluble deriva-
tives of endohedral metallofullerenes has played a key role in utilizing these compounds
for medicinal applications. In this context, gadolinium-encapsulated fullerenes have been
proposed as contrast agents to enhance MRI quality [137-142]. Another important rea-
son to use gadofullerenes as a contrast agent for MRI is to ensure that the metal atom is
held within the cage for applications that might require longer residency times. Toth et
al. [139] reported the nuclear magnetic relaxation profiles for two water-soluble function-
alized fullerenes: Gd@C
60
(OH)
x
and Gd@C
60
[C(COOH)
2
]
10
[139]. From their experimental
results, they have concluded that the strong pH dependency of the proton relaxivities
made these functionalized fullerenes great candidates for MRI contrast agents with a
stimulus based on pH. After this, in another study, Sitharaman et al. [140] showed that the
© 2011 by Taylor & Francis Group, LLC
