In Vivo Magnetic Resonance Detection of Cancer by Using Multifunctional Magnetic Nanocrystals

Huh, Yong Min; Jun, Young‐wook; Song, Ho Taek; Kim, Sungjun; Choi, Jin Woo; Lee, Jae Hyun; Yoon, Sarah; Kim, Kyung‐Sup; Shin, Jeon Soo; Cheon, Jinwoo

doi:10.1021/ja052337c

Cited by 826 publications

(518 citation statements)

References 27 publications

Supporting

Mentioning

502

Contrasting

Unclassified

Order By: Relevance

“…The superparamagnetic Fe 3 O 4 nanocrystals shortened the water proton spin-spin relaxation times, by perturbing the magnetic relaxation processes of the protons in the surrounding water molecules resulting in a decrease in the MRI signal intensity and consequent darkening of the MR images [65] and [66]. Relaxivities were calculated using the relaxation times and the concentrations obtained from inductively coupled plasma atomic emission spectroscopy (ICP-AES) measurements with each type of nanoparticles.…”

Section: Relaxivitymentioning

confidence: 99%

The cell labeling efficacy, cytotoxicity and relaxivity of copper-activated MRI/PET imaging contrast agents

et al. 2011

View full text Add to dashboard Cite

/npsi/ctrl?action=rtdoc&an=19739632&lang=en http://nparc.cisti-icist.nrc-cnrc.gc.ca/npsi/ctrl?action=rtdoc&an=19739632&lang=fr READ THESE TERMS AND CONDITIONS CAREFULLY BEFORE USING THIS WEBSITE.http://nparc.cisti-icist.nrc-cnrc.gc.ca/npsi/jsp/nparc_cp.jsp?lang=en Vous avez des questions? Nous pouvons vous aider. Pour communiquer directement avec un auteur, consultez la première page de la revue dans laquelle son article a été publié afin de trouver ses coordonnées. Si vous n'arrivez pas à les repérer, communiquez avec nous à PublicationsArchive-ArchivesPublications@nrc-cnrc.gc.ca. Questions?Contact the NRC Publications Archive team at PublicationsArchive-ArchivesPublications@nrc-cnrc.gc.ca. If you wish to email the authors directly, please see the first page of the publication for their contact information. NRC Publications Archive Archives des publications du CNRCThis publication could be one of several versions: author's original, accepted manuscript or the publisher's version. / La version de cette publication peut être l'une des suivantes : la version prépublication de l'auteur, la version acceptée du manuscrit ou la version de l'éditeur. For the publisher's version, please access the DOI link below./ Pour consulter la version de l'éditeur, utilisez le lien DOI ci-dessous.http://doi.org/10.1016/j.biomaterials.2010.10.013 Biomaterials, 32, 4, pp. 1167Biomaterials, 32, 4, pp. -1176Biomaterials, 32, 4, pp. , 2010 The cell labeling efficacy, cytotoxicity and relaxivity of copperactivated MRI/PET imaging contrast agents AbstractA new class of nanoparticle-based dual-modality positron emission tomography/magnetic resonance imaging (PET/MRI) contrast agents has been developed. The probe consists of a superparamagnetic iron oxide (SPIO) or manganese oxide core coated with 3,4-dihydroxy-d,l-phenylalanine (dl-DOPA). The chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was conjugated to DOPA termini. The DOTA modified nanoparticles allow chelation of copper for PET imaging. These surface functionalized nanoparticle-based probes have been characterized by various analytical techniques. The cell-labeling efficacy, cytotoxicity and relaxivity of these nanoparticles have been evaluated and compared with the same properties of one of the most commonly utilized MRI contrast agents, Feridex ® . Evidently, this new nanoparticle has a great potential for use in cell tracking with MRI and PET in the absence of transfecting agent. It is noteworthy that there is a sharp increase in r 2 relaxivity of these nanoparticles on coordination with Cu 2+ ions. Thus these iron oxide nanoparticles can also be explored as the smart magnetic resonance (MR) sensor for the detection of micromolar changes in copper concentration for neurodegenerative diseases such as Alzheimer's disease, Menkes and Wilson's diseases, amyotrophic lateral sclerosis and prion diseases.

show abstract

Section: Relaxivitymentioning

confidence: 99%

The cell labeling efficacy, cytotoxicity and relaxivity of copper-activated MRI/PET imaging contrast agents

et al. 2011

View full text Add to dashboard Cite

show abstract

“…[1][2][3][4] Targeted magnetic nanoparticles can be used to enhance the tissue contrast in magnetic resonance imaging (MRI), [5,6] to improve the efficiency in anticancer drug delivery, [7,8] and to eliminate tumor cells by magnetic fluid hyperthermia. [9][10][11] Recent synthetic progress makes it possible to produce mono disperse iron oxide nanoparticles with controlled sizes and magnetic properties, [12][13][14][15] but interactions between these nanoparticles and biomolecular entities, especially various tumor cells, are rarely studied owing to the challenge in nanoparticle functionalization and stabilization.…”

Section: Introductionmentioning

confidence: 99%

“…[9][10][11] Recent synthetic progress makes it possible to produce mono disperse iron oxide nanoparticles with controlled sizes and magnetic properties, [12][13][14][15] but interactions between these nanoparticles and biomolecular entities, especially various tumor cells, are rarely studied owing to the challenge in nanoparticle functionalization and stabilization. [6,16] Herein we report a robust surface-functionalization approach to link monodisperse Fe 3 O 4 nanoparticles with nuclear localization signal (NLS) peptide and test their capability in targeting tumor-cell nuclei. In vitro experiments showed that the uptake of the NLS-labeled nanoparticles by HeLa cells is increased by up to 233% over the non-NLS-labeled nanoparticles.…”

Section: Introductionmentioning

confidence: 99%

Monodisperse Magnetite Nanoparticles Coupled with Nuclear Localization Signal Peptide for Cell‐Nucleus Targeting

Xie

Kohler

et al. 2008

Chemistry An Asian Journal

View full text Add to dashboard Cite

Functionalization of monodisperse superparamagnetic magnetite (Fe 3 O 4 ) nanoparticles for cell specific targeting is crucial for cancer diagnostics and therapeutics. Targeted magnetic nanoparticles can be used to enhance the tissue contrast in magnetic resonance imaging (MRI), to improve the efficiency in anticancer drug delivery, and to eliminate tumor cells by magnetic fluid hyperthermia. Herein we report the nucleus-targeting Fe 3 O 4 nanoparticles functionalized with protein and nuclear localization signal (NLS) peptide. These NLS-coated nanoparticles were introduced into the HeLa cell cytoplasm and nucleus, where the particles were monodispersed and non-aggregated. The success of labeling was examined and identified by fluorescence microscopy and MRI. The work demonstrates that monodisperse magnetic nanoparticles can be readily functionalized and stabilized for potential diagnostic and therapeutic applications.

show abstract

“…There is a great deal of interest in enhancing the utility of these tools in medicine and research through the development of molecularly-targeted MRI contrast agents. One example might be a chimeric molecule comprised of a contrast agent tethered to a molecule capable of binding to a specific protein or other biomolecular target with high affinity and specificity [4][5][6][7][8][9][10][11][12][13][14][15][16][17]. For example, we previously reported that a peptide selected from a phage display library to bind the yeast Gal80 protein can be linked to GdDOTA to create a reagent capable of imaging Gal80 protein in vitro [18,19].…”

Section: Introductionmentioning

confidence: 99%

The detection limit of a Gd3+-based T1 agent is substantially reduced when targeted to a protein microdomain

Hanaoka

Lubag

Castillo-Muzquiz³

et al. 2008

Magnetic Resonance Imaging

View full text Add to dashboard Cite

Simple low MW chelates of Gd 3+ such as those currently used in clinical MR imaging are considered too insensitive for most molecular imaging applications. Here, we evaluated the detection limit of a molecularly targeted, low MW Gd 3+ -based, T 1 agent in a model where the receptor concentration was precisely known. The data demonstrate that receptors clustered together to form a microdomain of high local concentration can be imaged successfully even when the bulk concentration of the receptor is quite low. A GdDO3A-peptide identified by phage display to target the anti-FLAG antibody was synthesized, purified and characterized. T 1 weighted MR images were compared with the agent bound to antibody in bulk solution and with the agent bound to the antibody localized on agarose beads. Fluorescence competition binding assays show that the agent has a high binding affinity (K D = 150 nM) for the antibody while the fully bound relaxivity of the GdDO3A-peptide:anti-FLAG antibody in solution was a relatively modest 17 mM −1 s −1 . The agent:antibody complex was MR silent at concentrations below ~9 µM but was detectable down to 4 µM bulk concentrations when presented to antibody clustered together on the surface of agarose beads. These results provided an estimate of the detection limits for other T 1 -based agents with higher fully bound relaxivities or multimeric structures bound to clustered receptor molecules. The results demonstrate that the sensitivity of molecularly-targeted contrast agents depends on the local microdomain concentration of the target protein and the molecular relaxivity of the bound complex. A model is presented which predicts that for a molecularly targeted agent consisting of a single Gd 3+ complex with bound relaxivity of 100 mM −1 s −1 or, more reasonably, four tethered Gd 3+ complexes each having a bound relaxivity of 25 mM −1 s −1 , the detection limit of a protein microdomain is ~690 nM at 9.4T. These experimental and extrapolated detection limits are both well below current literature estimates and suggests that detection of low MW molecularly targeted T 1 agents is not an unrealistic goal.

show abstract

In Vivo Magnetic Resonance Detection of Cancer by Using Multifunctional Magnetic Nanocrystals

Cited by 826 publications

References 27 publications

The cell labeling efficacy, cytotoxicity and relaxivity of copper-activated MRI/PET imaging contrast agents

The cell labeling efficacy, cytotoxicity and relaxivity of copper-activated MRI/PET imaging contrast agents

Monodisperse Magnetite Nanoparticles Coupled with Nuclear Localization Signal Peptide for Cell‐Nucleus Targeting

The detection limit of a Gd3+-based T1 agent is substantially reduced when targeted to a protein microdomain

Contact Info

Product

Resources

About