Biomedical Engineering Reference
In-Depth Information
TABLE 9.1 (continued)
Toxicological Effects of Some Widely Used Nanoparticles
Health Effects
Type of NP
In Vitro
In Vivo
Fullerenes
Oxidative stress and genotoxicity [152,286,287]
Antibacterial activity through reactive oxygen species
production [288,289]
Increase in proinflammatory cytokines and Th1
cytokines in BAL fluid
Increased T-cell distribution in lungs
Elevated levels of 8-oxo-dG in the liver and lung
[249,265,290-294]
Source:
Adapted from Dhawan A, Sharma V.
Analytical and Bioanalytical Chemistry
. 2010;398(2):589-605. Epub
2010/07/24.
formation of a protein corona, when considering possible biointeractions [91]. As the nanoparticle
enters a biological solution, such as blood, it becomes coated with proteins from the serum. The pro-
teins may change their folding and confirmations as they interact with the nanoparticle, leading to
the exposure of new epitopes and, perhaps, altered function [92,93]. The composition of the proteins
would depend on the nature of the biological fluid, such that the blood, a high-protein environment,
would result in a different protein corona composition as compared with ocular fluid, a low-protein
environment [89]. The properties of the nanoparticle surface, as well as the properties of the pro-
teins, also play a role in determining the affinity and composition of protein binding in the corona.
The nanoparticle may already possess some of the ligands intentionally bound in the process of
synthesis or may have residues from the manufacturing process. Coupled with other properties of
nanoparticle surface, such as the degree of hydrophobicity, the nanoparticle's surface determines
the composition of its corona.
Once the nanoparticle comes into contact with a cell membrane, a whole new layer of complex-
ity arises, based on the properties of the membrane, such as its fluidity and thermodynamics, het-
erogeneous composition, and its high activity [94]. The specific mechanism of interaction depends
on the type and number of ligands present on the nanoparticle and the availability of the receptors
on the cell membrane. If endocytosis occurs, its mechanics, including the “wrapping time,” can
be described as a mathematical function of numerous factors pertaining to the components of the
process—the particle properties, such as particle size and shape; the environment properties, such
as the energy of the system; and the cell membrane properties, such as the rate of receptor diffusion
and elasticity of the membrane [68,95,96]. Penetration of the membrane does not solely occur based
on a receptor-mediated basis; charge-dependent reconstruction of the phospholipid bilayer has been
observed where negatively charged particles bind to liquid membrane and induce gelation, whereas
positively charged nanoparticles caused gelled areas to turn into a liquid state [97]. This enables
some cationic and gold nanoparticles with amphipathic properties to generate transient holes in the
membrane without disrupting the bilayer [66,98]. However, if the cationic properties are not tightly
controlled, the nanoparticles may cause disturbances of the membrane by altering its structure, as a
direct relationship of defects in the cell membrane and the concentration of nanoparticles has been
demonstrated in scientific reports [91,99]. Charged nanoparticles may result in the disruption of
membrane activities, such as depolarization [100] and transport processes [101].
A limited amount of information is available on the processes that occur after the nanoparticle
enters the cell (Figure 9.6). Reports have shown that nanoparticles retain high activity resulting in
effects on cytoplasmic proteins, mitochondria, and nucleus especially with genetic material. An
understanding in the area of distribution of nanoparticles in the cell is especially important for the
design of effective drug delivery methods. Based on uptake mechanisms, the nanoparticles may
become localized in specific cell compartments. For instance, a clathrin-dependent mechanism of
