Biomedical Engineering Reference
In-Depth Information
which must be administered slowly, the newer versions of USPIO particles (e.g.,
ferumoxytol) appear to be safe even when injected rapidly [2, 3], and consequently
dynamic intravascular blood fl ow measurements are possible when using these
agents. Hence, MNPs with a diameter
100 nm are currently and effectively uti-
lized in a variety of biomedical applications, and are becoming established prod-
ucts in many patients. In this chapter, attention is focused on the use of various
forms of MNPs, modifi ed for applications in cancer imaging and therapy.
During recent years, a considerable improvement has been achieved in the devel-
opment of MNPs, notably for biomedical applications. Indeed, they have become
important tools for diagnosis, imaging and therapy to prevent various diseases,
such as cancer, atherosclerosis, and diabetes, with almost 250 reports having been
made during the past two years. In this chapter, the aim is to update recent develop-
ments in MNPs, particularly in their use for cancer imaging and therapy. For this
purpose, the development scheme has been segregated into fi ve areas: (i) MNP
fabrication and surface modifi cation for cancer treatment; (ii) conjugation of
various cancer targeting agents on MNPs; (iii)
in vitro
and
in vivo
characterization
of cancer-targeting nanoparticles; (iv) the application of ligand-directed MNPs for
imaging and therapy; and (v) ligand-directed MNPs for focused hyperthermia.
Over the past two decades, iron oxide nanoparticles have been used in cellular
therapy, tissue repair, drug delivery, hyperthermia [4, 5] , MRI [6 - 8] for magnetic
resonance spectroscopy [9], for magnetic separation [10] and, more recently, as
sensors for metabolites and other biomolecules [11 - 13] . Recent research has
focused on the targeted delivery of iron oxide nanoparticles to sites of interest, and
this has been accomplished with peptides, antibodies, and small molecules. These
ligands have emerged from phage or small-molecule screens, or are based on
antibodies or aptamers. Secondary reporters and combined therapeutic molecules
have further opened potential clinical applications of these materials. The newer
generation of MNPs has been developed to target specifi c cell types and molecular
targets via such affi nity ligands when compared to the fi rst - generation nanopar-
ticles that were mostly nonspecifi c.
As noted above, several studies have demonstrated the successful biological
application of MNPs for drug delivery, molecular imaging, and targeted therapy.
Although many articles [14-17] relating to MNPs and their biological applications
have been produced, they provide very limited information with regards to applica-
tions in cancer. Hence, the aim of this chapter is to provide a comprehensive
update of the cancer-related applications of MNPs, including drug delivery,
imaging [including MRI, optical, nuclear, positron emission tomography (PET),
computed tomography (CT), and single photon emission computed tomography
(SPECT)], multimodal imaging, and therapy. The chapter is organized in three
sections. Initially, the synthesis and surface modifi cations of MNPs for biological
applications is outlined, including methods of fabrication, surface chemistry, and
physico-chemical characterization. Further, following details of the development
of MNPs as cancer diagnosis and imaging agents, after which an update is pro-
vided of the application of MNPs in cancer therapy, including cancer therapy,
hyperthermia and thermal ablation, and MNP-directed toxicity studies.
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