Biomedical Engineering Reference
In-Depth Information
FIGURE 9.4
(a) Nanoparticle interactions with their environment, (b) the formation of a protein corona
around the nanoparticle. (Reproduced with permission from Walczyk D et al. What the cell “sees” in biona-
noscience.
Journal of American Chemical Society
2010;132(16):5761-8.)
the interactions of nanoparticles with the lipids and protein receptors on the cell membrane are
highly dependent on the protein corona and the ability of the nanoparticle to adsorb the biological
molecules [82,83]. Thus, it is important to not only understand the structure and characterization of
the nanoparticles, but also its environment and its interactions with the environment [82,84].
Furthermore, the charge of the nanoparticle has a direct impact on its stability in solution.
Charged nanoparticles stay well suspended in a solution due to repulsive forces. Neutral nanopar-
ticles, however, have the longest half-life in the blood, as charged nanoparticles get quickly cleared
and may cause complications such as hemolysis and platelet coagulation [63]. However, the interac-
tions with blood cells may be more dependent on the functional groups on the nanoparticle surface
[85]. Thus, hemolysis is one of the aspects of nanotoxicology to be considered, although many
nanoparticles do not exhibit interactions with erythrocytes or hemolysis [62]. Overall, the half-life
property depends on interactions of the nanoparticles with immunoglobulin, lipoprotein, comple-
ment and coagulation factors, acute phase proteins, and metal-binding and sugar-binding proteins
[80,82]. Thus, PEGylation helps extend the half-life by limiting the interactions and preventing
detection by macrophages and the complement system [58,64,86]. The dimensions of nanoparticles
also impact the clearance rate. Studies have shown that rod-shaped nanoparticles circulate 10 times
longer than spherical nanoparticles, which may be related to the rate of cell uptake, as spherical
shape makes uptake more likely [87]. Size also plays a role in the clearance rate from the blood.
Kidneys, as one of the sites of major blood filtration in the body, quickly clear small nanoparticles
(less than 6 nm) [88]. The most important factor in the determination of biointeractions is the sur-
face of the nanoparticle. By specifying the materials from which the nanoparticle is made, the
biointeractions can be more controlled (Table 9.1).
9.2.3 N
aNopartIcle
B
IoINteractIoNs
aNd
M
echaNIsMs
of
t
oxIcIty
As the nanoparticle enters a biological system, it is bound to exert some effect on the system [89]. The
beauty of nanotechnology is that the manipulations of very specific aspects of the system can occur
on a very small scale to minimize nonspecific interactions and off-target actions. Nanomaterials
offer the potential to deliver nucleic acids for the modification or regulation of faulty pathways and
for the transcription of specific proteins. Small molecules can be shuttled to specific targets, such
as tumors, and natural barriers, such as the blood-brain barrier, can be overcome. Owing to their
surface area, nanoparticles are very reactive and may demonstrate toxicity at sufficient dosages and
accumulation, even if the material itself is not toxic [90].
The design of the nanomaterial plays a crucial role in determining its level of toxicity. As men-
tioned earlier, particle size and surface properties are crucial in determining the stability, transloca-
tion, and types of interactions in a biological system (Figures 9.4 and 9.5). However, it is necessary
to account for the interactions of the nanomaterials with their suspension medium, such as the
