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Review
. 2013 Oct;30(10):2445-58.
doi: 10.1007/s11095-013-0982-y. Epub 2013 Jan 24.

Magnetic nanoparticles for tumor imaging and therapy: a so-called theranostic system

Huining He  1 , Allan David, Beata Chertok, Adam Cole, Kyuri Lee, Jian Zhang, Jianxin Wang, Yongzhuo Huang, Victor C Yang
Affiliations
Review

Magnetic nanoparticles for tumor imaging and therapy: a so-called theranostic system

Huining He et al. Pharm Res. 2013 Oct.

Abstract

In this review, we discussed the establishment of a so-called "theranostic" system by instituting the basic principles including the use of: [1] magnetic iron oxide nanoparticles (MION)-based drug carrier; [2] intra-arterial (I.A.) magnetic targeting; [3] macromolecular drugs with unmatched therapeutic potency and a repetitive reaction mechanism; [4] cell-penetrating peptide-mediated cellular drug uptake; and [5] heparin/protamine-regulated prodrug protection and tumor-specific drug re-activation into one single drug delivery system to overcome all possible obstacles, thereby achieving a potentially non-invasive, magnetic resonance imaging-guided, clinically enabled yet minimally toxic brain tumor drug therapy. By applying a topography-optimized I.A. magnetic targeting to dodge rapid organ clearance of the carrier during its first passage into the circulation, tumor capture of MION was enriched by >350 folds over that by conventional passive enhanced permeability and retention targeting. By adopting the prodrug strategy, we observed by far the first experimental success in a rat model of delivering micro-gram quantity of the large β-galactosidase model protein selectively into a brain tumor but not to the ipsi- or contra-lateral normal brain regions. With the therapeutic regimens of most toxin/siRNA drugs to fully (>99.9%) eradicate a tumor being in the nano-molar range, the prospects of reaching this threshold become practically accomplishable.

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Figures

Fig. 1
Fig. 1
Schematic illustration of the proposed brain drug delivery
Fig. 2
Fig. 2
MRI scans showing MION accumulation in 9L gliosarcoma (a) with; (b) without magnetic targeting. Reprinted with permission from (32)
Fig. 3
Fig. 3
Plot showing linear correlation between the MRI-derived dR2 and ESR-determined MION quantity in excised tissue samples
Fig. 4
Fig. 4
MION concentration in excised tumor and contra-lateral brain tissues quantified by ESR spectroscopy. Data expressed as Mean + SE. n=6. Reprinted with permission from (32)
Fig. 5
Fig. 5
Models of: (a) original; (b) modified magnetic configurations with (c) and (d) of their respective topographic maps generated by the implemented magnetic setups. Typical axial MRI scans of the rat head acquired after magnetic targeting with: (e) original; and (f) modified magnetic setups. Reprinted with permission from (28).
Fig. 6
Fig. 6
(a) MRI head-scans of 9L-glioma bearing rats of: Left: intravenous (I.V.) and Right: carotid artery magnetic targeting; and (b) MION accumulation in tumor and contra- lateral brain tissues was measured by ESR; following IV and IA injection of PEI-MION32. Reprinted with permission from (47).
Fig. 7
Fig. 7
Excised tumors from mice treated, from top to bottom, with: Row#1: PBS; Row#2 & #4: free gelonin (100 µg); Row#3 & #5: TAT-Gel (100 µg Gel equivalent). Reprinted with permission from (30).
Fig.8
Fig.8
Histochemical analysis of cryo-sections from (T) tumor (Left); ipsilateral brain (Middle); and (63) contralateral brain (Right) regions (scale: 100 µm). Sections were stained with X-Gal. Inset: at higher magnitude (scale: 25µm); capillaries stained with Burrstone's Red.
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