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

• Published in: Pharmaceutical research 2013-10, Vol.30 (10), p.2445-2458
• Main Authors: He, Huining, David, Allan, Chertok, Beata, Cole, Adam, Lee, Kyuri, Zhang, Jian, Wang, Jianxin, Huang, Yongzhuo, Yang, Victor C.
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Brain cancer; Brain Neoplasms - drug therapy; Brain Neoplasms - pathology; Drug Carriers - administration & dosage; Drug Carriers - chemistry; Drug Carriers - pharmacokinetics; Drug Delivery Systems - methods; Expert Review; Humans; Injections, Intra-Arterial; Injections, Intravenous; Magnetic Resonance Imaging - methods; Magnetite Nanoparticles - administration & dosage; Magnetite Nanoparticles - therapeutic use; Medical imaging; Medical Law; Nanoparticles; Peptides; Pharmacology/Toxicology; Pharmacy; Tumors
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-013-0982-y

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.