Targeted magnetic iron oxide nanoparticles for tumor imaging and therapy

Abstract

Magnetic iron oxide (IO) nanoparticles with a long blood retention time, biodegradability and low toxicity have emerged as one of the primary nanomaterials for biomedical applications in vitro and in vivo. IO nanoparticles have a large surface area and can be engineered to provide a large number of functional groups for cross-linking to tumor-targeting ligands such as monoclonal antibodies, peptides, or small molecules for diagnostic imaging or delivery of therapeutic agents. IO nanoparticles possess unique paramagnetic properties, which generate significant susceptibility effects resulting in strong T2 and T*2 contrast, as well as T1 effects at very low concentrations for magnetic resonance imaging (MRI), which is widely used for clinical oncology imaging. We review recent advances in the development of targeted IO nanoparticles for tumor imaging and therapy.

Figure 1

Targeted IO nanoparticles for tumor imaging in vivo. The tumor-specific ligands/antibodies were conjugated to the surface of SPIO coated by PEG. Targeted IO nanoparticles accumulate in solid tumor tissue mainly by receptor-mediated endocytosis and are usually taken up by macrophages in the liver (Küpffer cells) and spleen.

Figure 2

MR images and their color maps. HER-MMPNs (a–d) and IRR(human IgG) -MMPNs (e–h) were injected into mice bearing NIH3T6.7 tumors at various time intervals: a, e) preinjection; b, f) immediately after; c, g) 1 h after; d, h) 12 h after injection of the MMPNs. i) ΔR₂/R₂^pre graph versus time before and after injection of MMPNs. j) Comparative therapeutic-efficacy study in an in vivo model. HER-MNPs (HER conjugated with a nondrug-loaded magnetic nanoparticle-polymer hybrid). Copyright © 2007. Reproduced with permission from Yang J, Lee CH, Ko HJ, et al 2007. Multifunctional magneto-polymeric nanohybrids for targeted detection and synergistic therapeutic effects on breast cancer. Angew Chem Int Ed Engl, 46:8836–9.

Figure 3

T2 maps of the mice bearing underglycosylated mucin-1 antigen (uMUC-1)- positive (LS174T) and uMUC-1-negative (U87) tumors. Transverse (top) and coronal (bottom) images showed a significant (52%; P < 0.0001) decrease in signal intensity in uMUC-1-positive tumors 24 hrs after administration of the CLIO-EPPT probe. Copyright ^© 2004. Reproduced with permission from Moore A, Medarova Z, Potthast A, et al 2004. In vivo targeting of underglycosylated MUC-1 tumor antigen using a multimodal imaging probe. Cancer Res, 64:1821–7.