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Targeted magnetic iron oxide nanoparticles for tumor imaging and therapy.

Peng XH, Qian X, Mao H, Wang AY, Chen ZG, Nie S, Shin DM - Int J Nanomedicine (2008)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology/Hematology, Emory University School of Medicine, Atlanta, GA 30322, USA.

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.

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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/R2pre 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.
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f2-ijn-3-311: 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/R2pre 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.

Mentions: The development of targeted IO nanoparticles for early tumor detection remains challenging. Underglycosylated mucin-1 antigen (uMUC-1) is an early tumor marker that is overexpressed on almost all human epithelial cell adenocarcinomas. Some important features render uMUC-1 a promising target for tumor imaging, 1) expressed in over 50% of all human cancers and remained homogeneously upregulated during the life growth of the tumor, 2) underglycosylated in tumor tissues but heavily glycosylated in normal tissues, make it possible to design probes that discriminate between normal and adenocarcinoma cells, 3) ubiquitously expressed on the cell surface, making it an accessible target for binding and imaging. Moore and colleagues (2004) synthesized EPPT1 peptide which specifically recognizes uMUC-1 and conjugated it to the dextran coat of crosslinked superparamagnetic iron oxide nanoparticles (CLIO). As shown in Figure 2, 24 hours after injection of targeted CLIO nanoparticles, a significant T2 signal reduction was observed in some regions of uMUC-1-positive LS174T tumors, while no significant change was seen in uMUC-1-negative U87 tumors. In addition, these results were further demonstrated by near-infrared fluorescence (NIRF) imaging. In this study, NIRF Cy5.5 dye-labeled CLIO nanoparticles were used both as MR- and NIRF-imaging contrast agent. This unique imaging probe produced a high-resolution signal on MR images and real-time NIRF imaging data, providing comprehensive information on tumor localization, environment, and status. This agent may have the potential to be applied for early tumor detection (Moore et al 2004).


Targeted magnetic iron oxide nanoparticles for tumor imaging and therapy.

Peng XH, Qian X, Mao H, Wang AY, Chen ZG, Nie S, Shin DM - Int J Nanomedicine (2008)

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/R2pre 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.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2626938&req=5

f2-ijn-3-311: 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/R2pre 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.
Mentions: The development of targeted IO nanoparticles for early tumor detection remains challenging. Underglycosylated mucin-1 antigen (uMUC-1) is an early tumor marker that is overexpressed on almost all human epithelial cell adenocarcinomas. Some important features render uMUC-1 a promising target for tumor imaging, 1) expressed in over 50% of all human cancers and remained homogeneously upregulated during the life growth of the tumor, 2) underglycosylated in tumor tissues but heavily glycosylated in normal tissues, make it possible to design probes that discriminate between normal and adenocarcinoma cells, 3) ubiquitously expressed on the cell surface, making it an accessible target for binding and imaging. Moore and colleagues (2004) synthesized EPPT1 peptide which specifically recognizes uMUC-1 and conjugated it to the dextran coat of crosslinked superparamagnetic iron oxide nanoparticles (CLIO). As shown in Figure 2, 24 hours after injection of targeted CLIO nanoparticles, a significant T2 signal reduction was observed in some regions of uMUC-1-positive LS174T tumors, while no significant change was seen in uMUC-1-negative U87 tumors. In addition, these results were further demonstrated by near-infrared fluorescence (NIRF) imaging. In this study, NIRF Cy5.5 dye-labeled CLIO nanoparticles were used both as MR- and NIRF-imaging contrast agent. This unique imaging probe produced a high-resolution signal on MR images and real-time NIRF imaging data, providing comprehensive information on tumor localization, environment, and status. This agent may have the potential to be applied for early tumor detection (Moore et al 2004).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology/Hematology, Emory University School of Medicine, Atlanta, GA 30322, USA.

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.

Show MeSH
Related in: MedlinePlus