Biomedical Engineering Reference
In-Depth Information
and cosmetics has substantially increased the potential for human skin exposure. Ag nanoparticle
crystals released from a commercial dressing were found to be toxic to both keratinocytes and
fibroblasts (Poon and Burd 2004). It is interesting to see that fibroblasts appeared to be more sensi-
tive to Ag nanoparticles than keratinocytes. Ag nanoparticles are found to induce cell death and
oxidative stress in human fibrosarcoma and skin carcinoma cells (Arora et al. 2008), and it was
demonstrated that Ag nanoparticles could enter cells and cause DNA damage and apoptosis in
fibroblasts and liver cells (Arora et al. 2009). The possible mechanism of Ag nanoparticle toxicity
in fibroblasts has been elaborated upon (Hsin et al. 2008) and Ag nanoparticles have been found to
induce ROS and release of cytochrome-c into the cytosol and the translocation of Bax proteins to
the mitochondria. These observations suggest that Ag nanoparticle-mediated apoptosis was mito-
chondria-dependent in fibroblasts. Some further observations have suggested that Ag nanoparticles
induce a p53-mediated apoptotic pathway through which most of the chemotherapeutic drugs trig-
ger apoptosis (Gopinath et al. 2010). It has been demonstrated by different studies that the lungs and
liver are major target tissues for prolonged Ag nanoparticle exposure (Takenaka et al. 2001; Sung
et al. 2008). The studies of Ag nanoparticles on rat liver cells have shown that a significant depletion
of the antioxidant, glutathione reduced the mitochondrial membrane potential and increased ROS
(Hussain et al. 2005). These findings suggested that Ag nanoparticle cytotoxicity is likely mediated
through oxidative stress in liver cells. The expression of genes associated with cell cycle progression
and apoptosis in human hepatoma cells was induced by a noncytotoxic dose of Ag nanoparticles
(Kawata et al. 2009). Choi et al. studied the liver toxicity of Ag nanoparticles in adult zebrafish,
where a number of cellular alterations, including the disruption of hepatic cell cords and apoptotic
changes, were observed. The DNA double-strand break marker γ-H2AX and the expression of the
p53 protein implied that Ag nanoparticles induced DNA damage. In addition, the p53-related pro-
apoptotic genes Bax, Noxa, and p21 were upregulated (Choi et al. 2010a,b).
Experimental results showed that Ag nanoparticles were more toxic to mitochondria than Mn
and Mn
2+
. These mitochondria seem to be sensitive targets of cytotoxicity and deposition in the
cytoplasm. In environmental aspects, silver leaks into the aquatic environment. 150,000 kg of silver
enters into the aquatic system every year from industries (Helinor et al. 2010).
14.2.3.3 Toxicity of Copper Nanoparticles
Despite an increasing application of copper nanoparticles, there is a serious deficiency of informa-
tion regarding their impact on human health and the environment. Copper is an essential trace ele-
ment capable of producing toxic effects in animals or humans when ingested acutely or chronically
(Bremner 1998). There are numerous data regarding the toxicity of copper compounds. Upon oral
exposure, the liver and kidneys remain sensitive targets of copper toxicity. The manifestation of
copper poisoning mainly includes drowsiness and anorexia in the early stages (Winge and Mehra
1990; Barceloux 1999) as well as acute tubular necrosis in the kidney and hepatocellular necro-
sis (Liu et al. 2004). Moreover, metabolic alkalosis and copper accumulation in the kidneys were
detected in mice that were orally exposed to nanocopper particles (Galhardi et al. 2004). Although
the potential risks of nanocopper particles on human health have been identified, its subacute toxic-
ity has not been depicted (Lei et al. 2008).
14.2.3.4 Toxicity of Dendrimer
The reported hepatotoxicity has been consistent with biodistribution studies that revealed high liver
accumulation for G3 (Generation 3) polyamidoamine dendrimers (IP) (Roberts et al. 1996), G3
and G4 polyamidoamine dendrimers (IV or IP) (Malik et al. 2000), biotinylated-polyamidoamine
dendrimers (G0-4) (IV) (Wilbur et al. 1998), and polyethylene glycol-polyester dendritic hybrids
(IV) (DeJesus et al. 2002). Roberts et al. observed the liver cell vacuolization of the cytoplasm in
a 6-month toxicity study group after administration of G7 polyamidoamine dendrimers by the I.P.
route once a week for 10 weeks (Roberts et al. 1996). A third-generation melamine dendrimer (MW
8067, 24 amine termini) was evaluated for
in vivo
acute toxicities (single dose, 48 h) and subchronic
