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Intelligent design of nano-scale molecular imaging agents.

ABSTRACT: Visual representation and quantification of biological processes at the cellular and subcellular levels within living subjects are gaining great interest in life science to address frontier issues in pathology and physiology. As intact living subjects do not emit any optical signature, visual representation usually exploits nano-scale imaging agents as the source of image contrast. Many imaging agents have been developed for this purpose, some of which exert nonspecific, passive, and physical interaction with a target. Current research interest in molecular imaging has mainly shifted to fabrication of smartly integrated, specific, and versatile agents that emit fluorescence or luminescence as an optical readout. These agents include luminescent quantum dots (QDs), biofunctional antibodies, and multifunctional nanoparticles. Furthermore, genetically encoded nano-imaging agents embedding fluorescent proteins or luciferases are now gaining popularity. These agents are generated by integrative design of the components, such as luciferase, flexible linker, and receptor to exert a specific on-off switching in the complex context of living subjects. In the present review, we provide an overview of the basic concepts, smart design, and practical contribution of recent nano-scale imaging agents, especially with respect to genetically encoded imaging agents.

SUBMITTER: Kim SB

PROVIDER: S-EPMC3546735 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Intelligent design of nano-scale molecular imaging agents.

Kim Sung Bae SB Hattori Mitsuru M Ozawa Takeaki T

International journal of molecular sciences 20121212 12

Visual representation and quantification of biological processes at the cellular and subcellular levels within living subjects are gaining great interest in life science to address frontier issues in pathology and physiology. As intact living subjects do not emit any optical signature, visual representation usually exploits nano-scale imaging agents as the source of image contrast. Many imaging agents have been developed for this purpose, some of which exert nonspecific, passive, and physical in ...[more]

PMID: 23235326

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Project description:BackgroundThe development of T1-T2 dual contrast agent (CA) favors the visualization of the lesion in a more accurate and reliable manner by magnetic resonance imaging (MRI). The relaxivity and the interference between T1 and T2 CA are the main concerns for their design.MethodsIn this work, we constructed an Fe3O4@mSiO2/PDDA/BSA-Gd2O3 nanocomplex where BSA-Gd2O3 NPs and Fe3O4 NPs were chosen as T1 and T2 MRI CAs and a 20 nm mesoporous silica (mSiO2) nanoshell was introduced to reduce the interference between them. We performed transmis sion electron microscopy, X-ray powder diffraction, UV-vis absorption spectra, and Fourier transform infrared absorption (FTIR) spectra to characterize the prepared nanocom-plex and MRI scanning to evaluate their MRI behaviors. Furthermore, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and hematologic and biochemical analyses were introduced to evaluate their in vitro and in vivo toxicity. Finally, the specific MRI of 786-0 cells with Fe3O4@mSiO2/PDDA/BSA-Gd2O3-AS1411 nanoprobe in vitro was realized. In vivo biodistribution of Fe3O4@mSiO2/PDDA/BSA-Gd2O3 nanocomplex in the mouse was determined by the quantification of the Gd element by inductively coupled plasma-mass spectrometry.ResultsThe prepared Fe3O4@mSiO2/PDDA/BSA-Gd2O3 nanocomplex possessed high longitudinal (r1=11.47 mM s-1 Gd) and transverse (r2=195.1 mM s-1 Fe) relaxivities, enabling its use as a T1-T2 dual contrast agent for MRI. MTT testing and hematologic and biochemical analysis indicated the good biocompatibility of Fe3O4@mSiO2/PDDA/BSA-Gd2O3 nanocomplex in vitro and in vivo. After further conjugation with AS1411 aptamer, they could target tumor cells successfully by T1 and T2 MRI in vitro. The possible metabolic pathway of the tail vein-injected Fe3O4@mSiO2/PDDA/BSA-Gd2O3 nanocomplex in mouse was mainly via kidney.ConclusionA T1-T2 dual-mode contrast agent, Fe3O4@mSiO2/PDDA/BSA-Gd2O3 nano-complex, was developed and its good performance for tumor cell targeting in vitro and kidney contrast-enhanced MRI in mice indicated its promising potential as an effective T1-T2 dual-mode contrast agent for in vivo MRI with self-confirmation.

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Intelligent design of nano-scale molecular imaging agents.

Publications

Intelligent design of nano-scale molecular imaging agents.

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