Biomedical Engineering Reference
In-Depth Information
oxygen species) were observed except for small oxidative DNA lesions.
186
One
study reported that by staining with crystal violet dye, the existence of gas ves-
icles in SPIONs-treated cells were observed with increased granularity of the
cells.
187
It was explained that such observation might have been the result of
autophagy that caused cytotoxicity.
It has been suggested that the proteins, which adsorb on the surface of NMs
including IOMNPs
188,189
can have significant impact on the NMs biological,
biochemical, and cellular behavior.
188
This nanoparticle-protein interaction is
now recognized as a key issue for defining the toxicity of NMs
188
because of
unfavorable changes in protein configurations that can lead to fibrillation, expo-
sure to new antigenic epitopes, and possible loss of protein function.
165,190
The
protein adsorption on IOMNPs can cause denaturation that can lead to the expo-
sure of new antigenic sites which can initiate a cascade of immune response.
190
Hence, the specific binding rates and affinities of different plasma proteins to
NMs have been the subject of some investigations.
191
They used size-exclusion
chromatography (SEC) to determine the affinity and stoichiometry of protein
bonded to particles, surface plasmon resonance (SPR) to get the rates of protein
association and dissociation; and isothermal titration calorimetry (ITC). The
quantity of the proteins adsorbed to NMs was the subject of the study by Lynch
et al.
192
In an in vitro study, exposing IOMNPs to cell medium for a period of 24 h
caused the proteins in the medium to coat the NMs creating the protein corona.
These protein coated NMs were then used for cell toxicity studies.
187
The results
indicated that the IOMNPs that were pre-coated with proteins from the cell
medium had significantly lower toxicity. In a biological unit like a cell, organ,
or tissue, the NMs are presented coated with the proteins that adsorbed along
the way before the NMs reached their target.
193
Another area of possible toxigenicity of IOMNPs as they move through
narrow capillaries is agglomeration that may lead to clogging (embolizations)
of small blood vessels. Thus, stabilization of IOMNPs is a critical matter in
their function as drug delivery vehicles. Considerations of the isoelectric point
around pH 7 which is same as that for biological fluids has to be taken into
account during the applications of IOMNPs in vivo.
194
By carefully choos-
ing the coating on the IOMNPs, colloidal stability can be imparted, thereby,
increasing the blood circulation half-life.
165
In addition, the particle size, size
distribution, shape, concentration/volume, stability of the drug/ferrofluid
binding (desorption characteristics), method of administration (oral, intra-
peritoneal, intra-muscular, etc.), duration/rate of the injection/infusion, and
strength/duration of the magnetic field applied are parameters to be considered
as well.
165
For personal medical applications, various patient-related parame-
ters such as weight, blood volume, cardiac output and systemic vascular resis-
tance, and tumor-related parameters such as circulation time, tumor volume
and location, vascular content of tumor, and blood flow in tumor must be taken
into consideration.
195
