Biomedical Engineering Reference
In-Depth Information
Opsonization and
recognition by
macrophages
Biological fate
Active
targeting
Cell-penetrating
peptide
Chemical design
Protein
adsorption
Antibody
Uncontrolled
aggregation
Inorganic
core
Organic or
inorganic
coating
Leakage
of toxic
components
Antifouling
coating
(PEG,
carbohydrates)
CB
VB
Passive targeting,
invisibility to RES/
furtivity
ROS
1
O
2
, HO
•
, O
2
-•
Oxidative
stress
FIGURE 1.13
Biological fate of nanomaterials. The top left scenario illustrates some of the effects of the pro-
tein adsorption on the nanoparticle surface. The top right scenario represents functionalization of the surface
with peptides and antibodies for uptake and cell penetration. The bottom right scenario demonstrates some of
the potential coatings for blocking the surface. The bottom left scenario shows dissolution and potential ROS
generation by the nanoparticle. (Reprinted with permission from Pelaz, B. et al. 2013.
Small
9(9-10):1573-84.)
stress, the upregulation of various inflammatory factors, such as redox-sensitive transcription fac-
tors (e.g., NF-κB), activator protein-1, and kinases, may induce or enhance inflammation (Lanone
and Boczkowski 2006, Rahman 2000, Rahman et al. 2005). There are several sources of free radical
origins, such as phagocytic cell responses to foreign materials, insufficient amounts of antioxidants,
the presence of transition metals, environmental factors, and physicochemical properties of some
NMs (Lanone and Boczkowski 2006). The effect of oxidative stress may extend to organs of the
RES, such as the liver, spleen, and organs of high blood flow, such as the lungs and kidneys, due to
the slow clearance and high tissue accumulation of potential free radicals from NMs. Intracellular,
NM interactions with cell components, such as mitochondria and nucleus, may result in the cascade
of events, such as the creation of ROS, cell cycle arrest, mutagenesis, apoptosis, and nuclear DNA
damage, all considered as main sources of toxicity (Aillon et al. 2009, Unfried et al. 2007). NMs
may be involved in the upregulation of free radical sources in macrophages and neutrophils (Lanone
and Boczkowski 2006). The immediate interaction of NMs with their surrounding environment
may result in hemolysis and thrombosis. In addition, NM interactions with the immune system have
been known to increase immunotoxicity (Dobrovolskaia and Mcneil 2007).
The adhesion of proteins on the surface of NMs is a normal physiological response in tackling
foreign bodies. Once attached to specific proteins (opsonization), the NP-protein complex is rec-
ognized by phagocytic macrophages. Once engulfed by macrophages, it is taken to the spleen or
the liver for its removal from the bloodstream (Owens and Peppas 2006). NMs can also interact
with other proteins not intended for opsonization. For example, the binding of human serum albu-
min or apolipoproteins promotes a prolonged circulation time in the blood (Ishida et al. 2001). As
mentioned earlier in the section, NM surface chemistry determines its interactions with different
moieties in the body. Positively charged particles attract proteins, leading to adsorption onto their
surfaces, and forming a complex known as a “protein corona.” These coronae can have multiple
layers: hard layers composed of proteins strongly attached to the surface of NMs, and dynamic,
