Biomedical Engineering Reference
In-Depth Information
oxygen species (ROS) but can be prevented by coating the IOMNPs with gold
168
preventing the formation of large aggregates.
One of the advantages of using NMs that are <100 nm in diameter is their
higher effective surface areas, lower sedimentation rates (or high stability in
suspension) and improved diffusion in tissues.
165
Particles that are <100 nm can
escape from the reticuloendothelial system (RES) more easily,
165
remain in the
circulation after injection and are capable of passing through the capillary sys-
tems of organs and tissues avoiding vessel embolism.
165
The size of the NMs
is equally important for achieving enhanced permeability and retention (EPR)
effect because particles larger than 10 nm cannot penetrate the endothelium at
physiological conditions but can pass in inflammation or tumor infiltration.
180
Systematic injection of drug-loaded NMs into the bloodstream may or may not
be able to perform their designed function depending upon their size, morphol-
ogy and surface charge. For instance, tissue macrophages (i.e. Kupffer cells in
the liver) are highly sensitive to invading microorganism and NPMs.
165,181
In
the bloodstream, the plasma proteins (opsonins) easily adsorb on the surface
of NMs depending on their sizes, surface charge, and morphology.
165
Various
authors have studied the protein adsorption on NPs either in vitro or in vivo.
176
Moghimi et al.
181
studied the opsonization process (adsorption of plasma pro-
tein) on NMs as a function of surface charge, size, and hydrophilicity/hydropho-
bicity. Their results showed that the smaller the size the higher the hydrophilicity
of the NMs, the more inefficient is the opsonisation process. Zhang et al.
176
reported that PEG and folic acid coating are most efficient for inhibiting protein
adsorption in vivo. The use of polymer coating,
Poly
{
3-(trimethoxy silyl pro-
pyl) methacrylate-r-polyethylene glycol methacrylate
}, on magnetite has been
reported to generate a stable, protein-resistant magnetic resonance imaging
probe.
182
They suggested that the polymer coating bestowed long-circulating
properties to the SPIONs in plasma allowing their escape from RES uptake by
macrophages.
RES uptake controls NMs with sizes above 200 nm or below 10 nm mak-
ing them unsuitable for drug delivery. It has been reported that NMs of
sizes between 10 and 100 nm can evade RES uptake and are therefore, most
effective for drug delivery purposes.
183
Furthermore, SPIONs with a posi-
tive charge showed higher internalization into human breast cancer cells
compared with negatively charged SPIONs but there was no difference in
the degree of internalization into Human Umbilical Vein Endothelian Cells
(HUVECs). This shows that the uptake pattern depends also on the cell
type.
184
Mouse fibroblast cells and human leukemia cells have been used to establish
the cytotoxicity of PVA-coated SPIONs with different shapes and morpholo-
gies (e.g. nanospheres, nanorods, nanoworms, magnetite colloidal nanocrystal
clusters, and nanobeads).
185
The results indicated that the SPIONs showed no or
little toxicity. In another study using human lung cancer cell line, 20 and 40 µg/
mL showed no DNA damage nor intracellular ROS (i.e. production of reactive
