Biomedical Engineering Reference
In-Depth Information
- Recognition of the nanosystems by the immune cells/macrophages (nanoparticle
coated by plasma proteins can promote their macrophage uptake and elimination
[
5
])
- Deposition of the nanosystems in non-macrophage cells
- Intracellular processing and activation of signaling pathways/apoptosis
Recently, Safi et al. [
11
] have studied the effects of aggregation and protein
corona on the cellular internalization of Ultra-small superparamagnetic iron oxide
(USPIO). They studied the influence of the coating by changing citrate ions
(low-molecular weight ligand) with small carboxylated polymers like polyacrylic
acid. The polymer-coated NPs showed a better stability and dispersibility without
the formation of protein corona. They also studied the interactions between
nanoparticles and human lymphoblastoid cells by TEM and flow cytometry. For
citrate-coated NPs, the kinetics of interactions with cells showed a more rapid
adsorption of USPIO on the cell membranes.
Tumor cell uptake of iron oxide nanoparticles in serum has been shown by
Moore et al. [
12
] to increase twofold over control particles. They identified fibro-
nectin, vitronectin, and complement C3 as the nanoparticle-bound proteins.
Chonn et al. [
13
] found a correlation between the absorption of beta-2-glycopro-
tein onto negatively charged liposomes and their liver clearance. Yan et al. [
14
]
tested the effect of beta-2-glycoprotein and apoE on the macrophage uptake of
negatively charged phosphatidylserine and phosphatidylglycerol liposomes (beta-
2-glycoprotein is known to adsorb onto negatively charged surfaces); the conclu-
sion was that these proteins do not affect the biodistribution to the liver
macrophages and hepatocytes. They found that primarily monosialoganglioside
(G
M1
) liposomes adsorb less protein such as IgG and C3 than other types of
liposomes. They showed a direct correlation between the amount of adsorbed
protein and the clearance times. Schreier et al. [
15
] observed that plasma fibronectin
is temporarily depleted following injection of large liposomes (500 nm) and
suggested the involvement of fibronectin in liposomal clearance.
The liposomes were found to be associated with high-density lipoprotein frac-
tion in the plasma. Pre-coating poly(methyl methacrylate) (PMMA) nanoparticles
with plasma has been shown to decrease their liver uptake in vivo, suggesting the
involvement of dysopsonins. The inhibitory effect of serum on the hepatic uptake of
liposomes is specific. Anionic liposomes coated with plasma or beta-2-glycoprotein
showed decreased uptake by the liver cells in vitro.
Human serum albumin (HSA), when adsorbed on the surface of polystyrene
microparticles, was reported to inhibit their phagocytosis by dendritic cells.
The fact that serum and plasma proteins often interfere, rather than promote
nanoparticle and liposome uptake, suggests that some of the uptake could be
mediated by means of direct recognition of the nanoparticle surface. Many types
of nanoparticles such as gold, silica, or liposomes can be taken up by macrophages
in the absence of serum. Macrophages are equipped with an effective system to
recognize nanoparticles even in the absence of opsonization signals. This hypothe-
sis is difficult to test in vivo in view of the constant presence of plasma proteins.
