Biomedical Engineering Reference
In-Depth Information
Many serum proteins have been found to bind to carbon black (CB), TiO
2
, or acrylamide NPs.
Among the proteins identified, many, such as apoliprotein E, granulocyte macrophage colony-stim-
ulating factor (GM-CSF), or transferrin, are ligands for cellular receptors. These proteins adsorbed
on the NP surfaces may contribute to the biological effects of NPs through activation/inactivation
of receptor-dependent signaling.
The amount (along with the functional and structural properties) of the adsorbed proteins deter-
mines the interactions of these nanomaterials with the cells and contributes to their biological
responses. These kinds of interactions mainly depend on the chemical nature, surface, and size of the
NPs. Another important consideration in this case may be the possibility of conformational changes
in the structure of adsorbed proteins. Such changes have been shown for a few NP types (e.g., Si NPs
induced a helical structure, including a catalytic site, on unstructured peptides in solution). Under
in
vivo
conditions, such interactions may cause a change or loss in function of the adsorbed proteins and
may also result in the presentation of novel peptide motifs to the immune system. In a recent publica-
tion, the authors speculated that such interactions can also lead to autoreactivity against self-epitopes
and may result in a persistent cell-mediated immune response, but further mechanistic studies are
needed to confirm such hypotheses [25]. Mainly proteins such as immunoglobulins and components
of the complement system are adsorbed from blood to the NP surface, which can act as signals for
innate and/or adaptive immune responses. Purified SWCNTs and double-walled CNTs (DWCNTs)
have been shown to activate the human serum complement system in a potent manner (comparable
to equal weight of zymosan) by the classical pathway of human serum complement activation [26].
Moreover, DWCNTs can also activate alternative pathways of complement activation. This activation
of complement may be due to selective binding of C1q CNTs (classical pathway activation), whereas
C3b binding may be postulated as the mechanism of alternative pathway activation.
The phenomenon of protein binding is important in immune responses, but the method to study
the phenomenon still remains unclear. A fundamental obstacle is the observation that the nature of
adsorbed proteins on the NPs also depends on the cell culture media.
20.13 LUNG TOXICITY
The liberation of fine CNPs in the atmosphere is a highly energy-exhaustive process and current
dosage and processes do not release significantly high amounts of airborne CNPs into the environ-
ment. However, there is a possible chance of health hazard upon cumulative accumulation effects,
especially when CNTs are handled in higher amounts. NPs may enter the body because of inhala-
tion, ingestion, cutaneous absorption, or through even the circulatory system. The respiratory sys-
tem is one of the most important systems identified for quick absorption and deposition of NPs in
the body. Owing to their small size, CNTs can be easily borne in air and be inhaled into the lungs
[27]. Therefore, pulmonary toxicity is of prime importance.
The potential mechanism of NP-induced pulmonary toxicity tentatively is explained in Figure
20.6. The initial acute inflammatory reaction is probably caused by damage to pulmonary epithelial
type I cells. The response includes robust neutrophilic pneumonia followed by recruitment and acti-
vation of macrophages. The unusual feature of the response is an early switch from the acute phase
response to events resulting from fibrogen with significant lung deposition of collagen and elastin.
This is accompanied by a characteristic change in the production and release of proinflammatory
(TNF-α, interleukin-1 h) to anti-inflammatory profibrogenic cytokines (TGF-b, interleukin-10).
Fibrogenic inflammatory responses were accompanied by a detrimental decrease in lung function
and increased susceptibility to infection [27].
Oxidative stress is a consistent measure for the evaluation of the toxic response in general. While
NPs enter into the lungs, oxidative stress tends to increase the formation of ROS, followed by
oxidation of lipids, and malondialdehyde (MDA) and glutathione (GSH) formation. Lung damage
is accompanied with an increase in MDA levels and a decrease in GSH (an antioxidant that helps
protect cells and tissues from ROS) levels [28].
