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Magnetic Nanoparticles for Tumor Imaging and Therapy: A So-Called Theranostic System

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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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Abbreviations

ADEPT:

antibody-directed enzyme prodrug therapy

ATTEMPTS:

antibody targeted, triggered, electrically modified prodrug type strategy

BBB:

blood–brain barrier

CPP:

cell-penetrating peptide

DDS:

drug delivery system

EPR:

enhanced permeability and retention

ESR:

electron spin resonance

GE:

gradient echo

I.A.:

intra-arterial

I.V.:

intravenous

LMWP:

low molecular weight protamine

MION:

magnetic iron oxide nanoparticles

MRI:

magnetic resonance imaging

PEI:

polyethyleneimine

β-Gal:

β-galactosidase

RES:

reticuloendothelial system

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ACKNOWLEDGMENTS AND DISCLOSURES

This work was supported in part by National Institutes of Health R01 Grants CA114612, NS066945, and a Hartwell Foundation Biomedical Research Award. This work was also partially sponsored by Grant R31-2008-000-10103-01 from the World Class University (WCU) project of South Korea. Victor C. Yang is currently a participating faculty member in the Department of Molecular Medicine and Biopharmaceutical Sciences, Seoul National University, South Korea. It was also partially supported by National Key Basic Research Program of China (2013CB932502), School of Pharmacy, Fudan University and The Open Project Program of Key Lab of Smart Drug Delivery (Fudan University), MOE and PLA, China (SDD2011-02).

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He, H., David, A., Chertok, B. et al. Magnetic Nanoparticles for Tumor Imaging and Therapy: A So-Called Theranostic System. Pharm Res 30, 2445–2458 (2013). https://doi.org/10.1007/s11095-013-0982-y

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