期刊
PHARMACEUTICAL RESEARCH
卷 30, 期 10, 页码 2445-2458出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-013-0982-y
关键词
brain tumor/cancer; cell-penetrating peptide; magnetic nanoparticles; theranostic system; tumor imaging and therapy
资金
- National Institutes of Health [CA114612, NS066945]
- Hartwell Foundation Biomedical Research Award
- World Class University (WCU) project of South Korea [R31-2008-000-10103-01]
- National Key Basic Research Program of China, School of Pharmacy, Fudan University [2013CB932502]
- Key Lab of Smart Drug Delivery (Fudan University)
- MOE
- PLA, China [SDD2011-02]
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 beta-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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