Biomedical Engineering Reference
In-Depth Information
with melphalan [328]. In the latter case, the resultant “magnetohydrodynamic
thermochemotherapy” produced a 30% regression of nonmetastatic tumors in
mice, with a resulting increase in the life-span of 290%.
A large number of studies into the application of static magnetic fi elds for posi-
tioning magnetic nanoparticles at the required site of action have been under-
taken. Most of these investigations have involved either the targeting of cells in
culture, or feasibility studies in animal models. A good example of targeting in
tumor models was recently reported [329] where MRI was used to confi rm the
migration of nanoparticles towards NdFeB magnets placed outside the peritoneal
cavity, above grafts of a human ovarian carcinoma. An excellent demonstration of
targeting in culture was provided by the group of Hyeon [330], where the uptake
of polymer nanoparticles was enhanced by the application of a magnetic fi eld,
when clusters of Fe
3
O
4
nanoparticles were loaded in doxorubicin-loaded polymer
nanoparticles. The polymer particles were composed of biodegradable poly(lactic-
co
-glycolic acid) (PLGA), surface-coated with PEGylated folate for the active target-
ing of cancer cells. Interest in these targeting applications also arises from the
possibility of detecting the particles after treatment, by MRI, and correlating the
results with any histological fi ndings [331] .
In fact, polymer/iron oxide composites are the most commonly reported
magnetic theranostic nanoparticles. A good recently described example [332]
was the development of functionalized linkers to couple to amino-polyvinyl
alcohol (aminoPVA), by amide linkages, to produce drug-functionalized-
aminoPVA-iron oxide nanocomposites, as vectors for drug delivery. Linkers were
developed to which the anti- cancer drugs 5 - fl uorouridine and doxorubicin
were attached as biologically labile esters or peptides, respectively. The former
proved to be viable delivery vehicles when tested using human melanoma cells
in culture, as they were taken up by the cells and proved to be effi cient anti - tumor
agents.
A fi nal class of therapeutic molecular/iron oxide composite involves the direct
binding of a molecule of interest to the nanoparticle. A prominent example here
[333] is the covalent linking of siRNA to magnetic nanoparticles labeled with a
near-infrared dye. This strategy has been shown to be feasible for monitoring the
effi ciency of siRNA delivery and silencing, which is a current requirement in the
development of cancer therapeutics.
Unfortunately, despite the obvious potential of a great many of these agents, the
vast majority will be applied only in drug development and basic research, or will
remain of academic interest only. Even with credible demonstrations of effi cacy,
in cellular or animal models, the pathway to use in humans is very long and
expensive. A premium is placed by industry on producing simple, easily scaleable
processes that are likely to result in new mass applications in medicine. Any
technology that fails by these demanding measures is unlikely to progress very
far, through the clinical and regulatory processes. It is likely, therefore, that con-
vergent approaches - developed by adopting standardized and perhaps regulatory
approved building blocks - could represent a shorter route to the clinic.
