Biomedical Engineering Reference
In-Depth Information
TABLE 3.10
Studies Concentration and Drug-Loading-Dependent Toxicity
Type of
Nanoparticle
Toxicity/Organ
Affected
Mechanism Involved/Results
Reference
Nanoparticles
—
High concentration of nanoparticles would
promote particle aggregation and therefore
reduce toxic effects compared to lower
concentrations; aggregation of nanoparticles is
essential in determining their toxicity, due to a
more effective macrophage clearance for
larger particles compared to smaller ones
Gurr et al. (2005)
Takenaka et al. (2001)
Churg et al. (1998)
Gold nanoparticles
Reduce viability
and reproductive
performance
Naked nanoparticle cause biomolecule
interactions and alteration of downstream
process
Vecchio et al. (2012)
Starch-coated
silver nanoparticle
Cytotoxicity and
genotoxicity
Reduce ATP content of cell, damage to
mitochondria, increased production of ROS
Asharani et al. (2009)
toxic than larger particles of the same, insoluble material when compared by mass. Surface area
was, therefore, a driver for inflammation from these materials; the differences in severity of the
response disappeared when the dose was expressed as the surface area. These examples emphasize
the importance of particle size, and, by implication, the surface area that is presented to the bio-
logical system to induce particle toxicity (SCENIHR/002/05). Indeed, smaller nanoparticles have
higher surface areas and particle numbers per unit mass compared to larger particles. A larger
surface area leads to an increased reactivity (Roduner 2006) and is an increased source of ROS, as
demonstrated by
in vitro
experiments (Donaldson and Stone 2003).
3.5.5 M
aterIal
c
oMposItIoN
-d
epeNdeNt
t
oxIcIty
The type and composition of the material used to prepare nanoparticles is also responsible for its
nanotoxicity. The examples are metal-, metal oxide-, and carbon-based nanoparticles. These mate-
rials are representative of each of the three most common and widely studied nanoparticle classes.
Generally, cells exposed to metal (e.g., Ag) nanoparticles show increased indications of cellular
stress and functional changes. The cellular toxicity of TiO
2
nanoparticles is due to its crystallinity,
oxidizing potential, and aggregation properties. For carbon-based nanoparticles, investigators gen-
erally agree that they are toxic and adversely affect a variety of cells due to factors such as metal
impurities, particulate states, structural differences, and the surface properties of CNTs, which
greatly influence their apparent cytotoxicity (Table 3.12). To advance the field, both through mate-
rial characterizations of nanoparticles prior to toxicity studies and standardized, reliable methods to
assess the cytotoxicity of materials are needed (Sara et al. 2012).
3.5.6 B
Io
-p
ersIsteNce
-d
epeNdeNt
t
oxIcIty
The dose of nanoparticles retained in the respiratory tract is expressed as the initial number of
deposited particles minus the number of particles subjected to clearance, which can occur by both
physicochemical and physiological processes. Clearances are believed to occur by the following
major mechanisms: (1) through the mucociliary escalator in the nose and tracheobronchial region,
(2) phagocytosis by alveolar macrophages, (3) dissolution, and (4) translocation. Nanoparticles that
cannot be cleared by any of these processes are considered to be biopersistent and are predicted to
accumulate during chronic exposures (Sanchez et al. 2009) (Table 3.13).
