Gadolinium-encapsulating iron oxide nanoprobe as activatable NMR/MRI contrast agent. 2012

Santimukul Santra, and Samuel D Jativa, and Charalambos Kaittanis, and Guillaume Normand, and Jan Grimm, and J Manuel Perez
Nanoscience Technology Center and Chemistry Department, University of Central Florida, 12424 Research Parkway, Suite 400, Orlando, Florida 32826, USA.

Herein we report a novel gadolinium-encapsulating iron oxide nanoparticle-based activatable NMR/MRI nanoprobe. In our design, Gd-DTPA is encapsulated within the poly(acrylic acid) (PAA) polymer coating of a superparamagnetic iron oxide nanoparticle (IO-PAA), yielding a composite magnetic nanoprobe (IO-PAA-Gd-DTPA) with quenched longitudinal spin-lattice magnetic relaxation (T(1)). Upon release of the Gd-DTPA complex from the nanoprobe's polymeric coating in acidic media, an increase in the T(1) relaxation rate (1/T(1)) of the composite magnetic nanoprobe was observed, indicating a dequenching of the nanoprobe with a corresponding increase in the T(1)-weighted MRI signal. When a folate-conjugated nanoprobe was incubated in HeLa cells, a cancer cell line overexpressing folate receptors, an increase in the 1/T(1) signal was observed. This result suggests that, upon receptor-mediated internalization, the composite magnetic nanoprobe degraded within the cell's lysosome acidic (pH 5.0) environment, resulting in an intracellular release of Gd-DTPA complex with subsequent T(1) activation. In addition, when an anticancer drug (Taxol) was coencapsulated with the Gd-DTPA within the folate receptor targeting composite magnetic nanoprobe, the T(1) activation of the probe coincided with the rate of drug release and corresponding cytotoxic effect in cell culture studies. Taken together, these results suggest that our activatable T(1) nanoagent could be of great importance for the detection of acidic tumors and assessment of drug targeting and release by MRI.

UI MeSH Term Description Entries
D008279 Magnetic Resonance Imaging Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. Chemical Shift Imaging,MR Tomography,MRI Scans,MRI, Functional,Magnetic Resonance Image,Magnetic Resonance Imaging, Functional,Magnetization Transfer Contrast Imaging,NMR Imaging,NMR Tomography,Tomography, NMR,Tomography, Proton Spin,fMRI,Functional Magnetic Resonance Imaging,Imaging, Chemical Shift,Proton Spin Tomography,Spin Echo Imaging,Steady-State Free Precession MRI,Tomography, MR,Zeugmatography,Chemical Shift Imagings,Echo Imaging, Spin,Echo Imagings, Spin,Functional MRI,Functional MRIs,Image, Magnetic Resonance,Imaging, Magnetic Resonance,Imaging, NMR,Imaging, Spin Echo,Imagings, Chemical Shift,Imagings, Spin Echo,MRI Scan,MRIs, Functional,Magnetic Resonance Images,Resonance Image, Magnetic,Scan, MRI,Scans, MRI,Shift Imaging, Chemical,Shift Imagings, Chemical,Spin Echo Imagings,Steady State Free Precession MRI
D009682 Magnetic Resonance Spectroscopy Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING). In Vivo NMR Spectroscopy,MR Spectroscopy,Magnetic Resonance,NMR Spectroscopy,NMR Spectroscopy, In Vivo,Nuclear Magnetic Resonance,Spectroscopy, Magnetic Resonance,Spectroscopy, NMR,Spectroscopy, Nuclear Magnetic Resonance,Magnetic Resonance Spectroscopies,Magnetic Resonance, Nuclear,NMR Spectroscopies,Resonance Spectroscopy, Magnetic,Resonance, Magnetic,Resonance, Nuclear Magnetic,Spectroscopies, NMR,Spectroscopy, MR
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D003287 Contrast Media Substances used to allow enhanced visualization of tissues. Radiopaque Media,Contrast Agent,Contrast Agents,Contrast Material,Contrast Materials,Radiocontrast Agent,Radiocontrast Agents,Radiocontrast Media,Agent, Contrast,Agent, Radiocontrast,Agents, Contrast,Agents, Radiocontrast,Material, Contrast,Materials, Contrast,Media, Contrast,Media, Radiocontrast,Media, Radiopaque
D005682 Gadolinium An element of the rare earth family of metals. It has the atomic symbol Gd, atomic number 64, and atomic weight 157.25. Its oxide is used in the control rods of some nuclear reactors.
D006367 HeLa Cells The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for, among other things, VIRUS CULTIVATION and PRECLINICAL DRUG EVALUATION assays. Cell, HeLa,Cells, HeLa,HeLa Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D053769 Nanocapsules Nanometer-sized, hollow, spherically-shaped objects that can be utilized to encapsulate small amounts of pharmaceuticals, enzymes, or other catalysts (Glossary of Biotechnology and Nanobiotechnology, 4th ed). Nanocapsule
D058185 Magnetite Nanoparticles Synthesized magnetic particles under 100 nanometers used in many biomedical applications including DRUG DELIVERY SYSTEMS and CONTRAST AGENTS. The particles are usually coated with a variety of polymeric compounds. Magnetite SPIONs,Magnetite Superparamagnetic Iron Oxide Nanoparticles,Superparamagnetic Magnetite Nanoparticles,Magnetite Nanoparticle,Magnetite Nanoparticle, Superparamagnetic,Magnetite Nanoparticles, Superparamagnetic,Magnetite SPION,Nanoparticle, Magnetite,Nanoparticle, Superparamagnetic Magnetite,Nanoparticles, Magnetite,Nanoparticles, Superparamagnetic Magnetite,SPION, Magnetite,SPIONs, Magnetite,Superparamagnetic Magnetite Nanoparticle
D032383 Myocytes, Cardiac Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC). Cardiomyocytes,Muscle Cells, Cardiac,Muscle Cells, Heart,Cardiac Muscle Cell,Cardiac Muscle Cells,Cardiac Myocyte,Cardiac Myocytes,Cardiomyocyte,Cell, Cardiac Muscle,Cell, Heart Muscle,Cells, Cardiac Muscle,Cells, Heart Muscle,Heart Muscle Cell,Heart Muscle Cells,Muscle Cell, Cardiac,Muscle Cell, Heart,Myocyte, Cardiac

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