Biomedical Engineering Reference
In-Depth Information
soft layers containing proteins, which are weakly adsorbed onto the surface (Mahmoudi et al.
2011). This NM-protein interaction can lead to the blockage of the protein's active site, mild con-
formational changes, or even denaturation. This can lead to a failure in the protein's ability to per-
form its normal biological function, such as cell signaling (Lynch and Dawson 2008, Mahmoudi
et al. 2011).
Ligand-coated NPs bind to cell receptors and can be endocytosed within the cell or trigger a
signaling cascade in the cell. Once inside the cell, the NMs are trapped within endolysosomal
vesicles. The exact mechanism of how they escape these vesicles remains unclear. However, once
that happens, they can be released into the cytosol where they can interact with other cell organelles,
including the nucleus.
1.6.2.2 Pharmacokinetics
Determining the pharmacokinetics of NMs is the first crucial step in understanding its biological
safety and toxicity. Pharmacokinetics is defined as the study of the mechanisms of absorption, dis-
tribution, metabolism, and excretion of a drug or its metabolite (ADME). A thorough, quantitative,
pharmacokinetic analysis of NMs would reveal the target cells, tissues, or organs; the residence
time; and the time and dose required to manifest toxicity. This information can be utilized to plan
various focused studies that involve only the target cell, eventually helping to decipher the molecu-
lar basis of toxicity. The pharmacokinetic behavior of NMs cannot be analyzed at present due to
the lack of data and the fact that any difference in the physicochemical properties might affect its
pharmacokinetics.
1.6.2.2.1 Absorption
NMs can enter the human body through different routes of exposure, such as the skin, lungs, and
gastrointestinal tract (GIT). As they pass through various parts of the body, they pick up differ-
ent biomolecules (Mahmoudi et al. 2011) described in the previous sections (Figure 1.13). The
absorption of biomolecules onto their surfaces determines their subsequent biological activities
in the body (Lynch and Dawson 2008). As mentioned previously, NMs interact with proteins to
form protein coronae, which determine their biodistribution and fate within the body. Protein
function is altered by the conformational changes induced by adsorption onto the surfaces of NMs
(Darlington et al. 2009, Lundqvist et al. 2004), which, in turn, affects their fate (Ishida et al. 2001,
Paciotti et al. 2004).
1.6.2.2.2 Distribution
After absorption, NMs can be distributed to various organs, tissues, and cells. It is difficult to
predict the behavior of NMs within living systems, owing to different variants within the systems.
The extent of NM distribution within the body depends upon the permeability of blood vessels.
Organs such as the liver, spleen, lymph nodes, and bone marrow can take up NMs. These organs
contain macrophages and form the RES or mononuclear phagocyte system (MPS). This system is
involved in the uptake and metabolism of foreign molecules (Saba 1970). Coatings on NMs can
affect their uptake. For example, NMs coated with polyethylene glycol (PEG) resist RES uptake
(Paciotti et al. 2004). It is therefore imperative to understand and study the distribution of NMs
within the body.
1.6.2.2.3 Metabolism
There are limited reports on NM metabolism. There are some NMs that degrade in the tissues, such
as polymer-based NMs and superparamagnetic iron oxide NMs. On the other hand, there are some
that show no degradation
in vivo
, such as QDs, fullerenes, and silica NMs (Ballou et al. 2004, Khan
et al. 2005, Singh et al. 2006, Yang et al. 2007). A study finding that CNTs can be degraded by
neutrophil myeloperoxidase provides evidence that suggests enzymatic metabolization of NMs to a
certain extent (Kagan et al. 2010). Also, coatings such as proteins used for QDs can be metabolized
