Iron Oxide Nanoparticles and Derivatives for Biomedical Imaging and Application in Cancer Diagnosis and Therapy - Bioanalysis Advanced Materials Methods and Devices - page 11

Fig. 1.5 Therapeutic MN-siSurvivin delivery. ( a ) In vivo MRI of mice bearing subcutaneous
LS174T human colorectal adenocarcinoma ( arrows ). The significant drop in T2 relaxation times
observed after administration of the nanoparticles indicated probe delivery. ( b ) The delivery of the
probe to tumors was confirmed by the high-intensity NIRF signal on in vivo optical images of mice
after injection of nanoparticles ( left , white light; middl e, NIRF; right , color-coded overlay). ( c )
Quantitative RT-PCR analysis of survivin expression in LS174T tumors after injection of mag-
netic nanoparticles conjugated to anti-Survivin siRNA. ( d ) Apoptotic rates in tumor tissues. Note
distinct areas with a high density of apoptotic nuclei ( green ) in tumors treated with probe ( left ),
which were not observed in tumors treated with the control magnetic nanoparticles (right). ( e )
H&E staining of frozen tumor sections revealed considerable eosinophilic areas of tumor necrosis
(N) in tumors treated with probe ( left ). Tumors treated with magnetic nanoparticles were devoid of
necrotic tissue ( right ). Purple hematoxiphilic regions (V) indicate viable tumor tissues. Scale bar,
50 m m (reprinted from [ 21 ] with permission from Nature Publishing Group)
prostate, brain, etc. [ 18 ]. In a recent study, authors injected porphyrin functionalized
bimagnetic nanoparticles targeting drug resistant melanoma in mice [ 2 ]. Porphyrin
functionalization is important because the constant need for porphyrins by cancer cells
due to their elevated sugar metabolism results in higher porphyrin uptake by tumor
cells. With the targeting porphyrin group on the surface of the nanoparticles, the
uptake by healthy cells isminimized. In vivo, mice carrying a subcutaneousmelanoma
xenograft were used. After intratumoral injection of nanoparticles and the application
of alternating magnetic field (AMF) pulses, the authors observed an 11 Cincreasein
temperature in the tumors and a significant decrease in tumor size. After intravenous
injection of the nanoparticles, the tumor size also decreased dramatically, representing
a more clinically relevant treatment scenario.
This approach has also been applied clinically. Patients with recurrent glioblas-
toma multiforme were treated with hyperthermia using magnetic nanoparticles as
heat generating probes [ 19 ]. Currently the only hyperthermia method that is consid-
ered involves local injection of nanoparticles into the tumor, which then is exposed
to an external alternating magnetic field [ 18 ]. This approach, however, can be made
more specific by incorporating targeting moieties into the nanoparticles.