Investigators are just beginning to use hyperthermia generated by alternating magnetic field (AMF) activated iron
oxide nanoparticles (IONPs) as a promising avenue for targeted cancer therapy. An important step in understanding
cell death mechanisms in nanoparticle AMF treatments is to determine the location of these nanoparticles in relation
to cellular organelles. In this paper, we report on transmission electron microscopy (TEM) studies designed to define
the position of 100 nm diameter dextran-coated iron oxide nanoparticles in murine breast adenocarcinoma (MTG-B)
and human colon adenocarcinoma tumors propagated in mice.
METHODS: Iron oxide nanoparticles (5 mg/g tumor) were injected into intradermal MTG-B flank tumors on female
C3H/HEJ mice and into HT-29 flank tumors on female Nu/Nu mice. The IONPs were allowed to incubate for
various times. The tumors were then excised and examined using TEM.
RESULTS: In the MTG-B tumors, most of the nanoparticles reside in aggregates adjacent to cell plasma membranes
prior to three hours post-injection. By four hours post injection, however, most of the nanoparticles have been
endocytosed by the cells. At time periods after four hours post injection, few visible extracellular nanoparticles
remain and intracellular nanoparticles have densely aggregated within endosomes. In the HT-29 tumor, however,
endocytosis of nanoparticles has not progressed to the same extent as in the MTG-B tumors by four hours post
CONCLUSIONS: The time at which most of the nanoparticles transition from being extracellular to intracellular in
the MTG-B system appears to be between two and four hours. The HT-29 cells, however, display different and
delayed uptake pattern. These data show that there are IONP uptake differences between tumor types (cell lines) and
that, based on known uptake kinetics, nanoparticle hyperthermia can be employed as an extracellular or intracellular
modality. These data will be important in guiding future nanoparticle hyperthermia cancer treatments.