Biomedical Engineering Reference
In-Depth Information
available on a commercial basis. Nevertheless, a number of challenges remain to
be addressed before the potential of technologies using MNPs can be fully realized
for biomedical applications, such as targeted MR imaging, drug/gene delivery, and
hyperthermia for cancer diagnosis and treatment. The increase in uniformity and
relaxivity of MNPs will improve MRI sensitivity, and MnFe
2
O
4
nanoparticles with
r
2
relaxivities signifi cantly higher than those of conventional crosslinked iron oxide
MR contrast agents have been reported [111]. Improvements in contrast agents
can be expected to lead to signifi cant enhancements in MRI due to the lower
inherent sensitivity of the technique as compared to optical imaging and positron
emission tomography [112]. As newer types of MNP with more favorable physico-
chemical properties continue to be developed, their nonspecifi c toxicological
aspects must also be minimized. The toxicity of nanoparticles may be the result
of many factors, including their size, chemical composition, biodegradability and
surface chemistry; indeed, the surface modifi cations of nanoparticles may play a
clear role in minimizing their toxicological effects [41].
The active targeting of MNPs against specifi c biomolecules on tumors will result
in a higher accumulation of MNPs at the disease sites, and thus allow an enhanced
detection contrast and sensitivity. The ability to target small and early- stage tumors
will be highly advantageous, as an early and accurate diagnosis can greatly increase
the probability of successful treatment. Furthermore, those MNPs accumulated in
tumor cells may also serve as a heating agent in magnetic fl uid hyperthermia to
allow the localized treatment of tumors. Consequently, the development of target
recognition moieties and strategies to couple these moieties to the MNPs, without
degrading their functions, represent critical factors for achieving these desired
treatment strategies. The functionalized MNPs must also meet further require-
ments, in that they are not taken up to any signifi cant degree by normal tissue
cells and macrophages. Multimodality treatments which combine targeted chemo-
therapy and magnetically mediated hyperthermia may also bring about synergistic
effects; for example, when MNPs are positioned in or close to cancer cells, they
may act both as a chemotherapeutic drug carrier and as a heating agent in the
presence of a magnetic fi eld. Any drug transported by the MNPs to the cancer cell
must retain its biological activity and be released at the target site. For this, the
use of heat-labile linkers to conjugate the drug to the MNP will offer another
degree of control for the release of drugs through heating of the MNPs using
external magnetic fi elds.
The large volume of research on MNPs which has been carried out during the
past few years has produced many encouraging results relating to the application
of MNPs as a targeting, imaging, and heating agents in the treatment of cancer.
However, it is important also to realize the limitations of these investigations, and
in particular the problems associated with scaling up from
in vitro
studies, via
animal models, to human applications. There is, nonetheless, a strong impetus
for interdisciplinary research into MNPs which will surely bring about improve-
ments in both experimental and materials design in order to meet these chal-
lenges. Clearly, new opportunities for the use of these nanoparticles for biomedical
applications are to be expected in the near future.
