Current state and future applications of active targeting in malignancies using superparamagnetic iron oxide nanoparticles.
Superparamagnetic iron oxide nanoparticles (SPIO) are novel MRI contrast agents. After cellular uptake, SPIO cause a negative T2 contrast in MRI. Passive targeting strategies rely on SPIO uptake in reticuloendothelial cells by receptor-mediated phagocytosis. Active targeting employs SPIO-conjugates with specific targeting ligands which selectively bind to biomarkers on target cells. Several receptor systems are overexpressed in cancerous diseases and have been investigated as targets for ligand-directed SPIO. Targeting receptors undergo repeated recycling to the cell surface and internalization and bind further SPIO, thereby amplifying the magnetic signal. Malignant cell degeneration may also lead to loss of specific receptor activity. SPIO-conjugates directed at those receptors lead to a prominent reduction in signal intensity in healthy tissue but not the tumor. These strategies allow for molecular profiling of target cells and potentially enable the early detection of malignant diseases, more accurate staging, and treatment monitoring. With the advent of multimodality imaging techniques like targeted nanoparticle-enhanced MRI and near infrared optical fluorescence imaging, the combined advantages of different systems can be exploited.
Center for Molecular Imaging Research, Charlestown, Massachusetts, USA. islam.tina@mgh.harvard.edu
Tina
T
Islam
Lee
L
Josephson
D002352:Carrier Proteins / Q000032:analysis; D003287:Contrast Media; D003911:Dextrans; D052203:Ferrosoferric Oxide; D058973:Folate Receptors, GPI-Anchored; D006801:Humans; D016023:Integrins / Q000032:analysis; D007501:Iron; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D053758:Nanoparticles; D036103:Nanotechnology; D009369:Neoplasms / Q000175:diagnosis*; D010087:Oxides; D011956:Receptors, Cell Surface / Q000032:analysis; D011990:Receptors, Transferrin / Q000032:analysis; D012697:Serine Endopeptidases / Q000032:analysis
D002352:Carrier Proteins; D003287:Contrast Media; D003911:Dextrans; D058973:Folate Receptors, GPI-Anchored; D016023:Integrins; D058185:Magnetite Nanoparticles; D010087:Oxides; D011956:Receptors, Cell Surface; D011990:Receptors, Transferrin; C097921:ferumoxtran-10; D007501:Iron; D012697:Serine Endopeptidases; C055645:hepsin; D052203:Ferrosoferric Oxide