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WIREs Nanomed Nanobiotechnol
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Functional mesoporous silica nanoparticles for bio‐imaging applications

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Biomedical investigations using mesoporous silica nanoparticles (MSNs) have received significant attention because of their unique properties including controllable mesoporous structure, high specific surface area, large pore volume, and tunable particle size. These unique features make MSNs suitable for simultaneous diagnosis and therapy with unique advantages to encapsulate and load a variety of therapeutic agents, deliver these agents to the desired location, and release the drugs in a controlled manner. Among various clinical areas, nanomaterials‐based bio‐imaging techniques have advanced rapidly with the development of diverse functional nanoparticles. Due to the unique features of MSNs, an imaging agent supported by MSNs can be a promising system for developing targeted bio‐imaging contrast agents with high structural stability and enhanced functionality that enable imaging of various modalities. Here, we review the recent achievements on the development of functional MSNs for bio‐imaging applications, including optical imaging, magnetic resonance imaging (MRI), positron emission tomography (PET), computed tomography (CT), ultrasound imaging, and multimodal imaging for early diagnosis. With further improvement in noninvasive bio‐imaging techniques, the MSN‐supported imaging agent systems are expected to contribute to clinical applications in the future. This article is categorized under: Diagnostic Tools > In vivo Nanodiagnostics and Imaging Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Schematic illustration of various imaging applications including optical imaging, magnetic resonance imaging (MRI), positron emission tomography (PET), computed tomography (CT), and ultrasound imaging by using mesoporous silica nanoparticle (MSN) support
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Functional mesoporous silica nanoparticles (MSNs) for multimodal imaging applications. (a) Schematic illustration for the preparation and surface functionalization of core–shell structural ZGOCS@MSNs@Gd2O3‐poly(ethylene glycol) (PEG) in which the role of ZGOCS (ZnGa2O4:Cr3+, Sn4+ structure) and Gd2O3 is luminescence and T1 magnetic resonance imaging (MRI) contrast agent, respectively. (b) in vivo T1‐weighted MR images (upper) and color‐weighed images (lower) of the mouse before and after intravenous injection of ZGOCS@MSNs@Gd2O3‐PEG. (c) in vivo imaging of a mouse at 1 min after intravenously injected with ZGOCS@MSNs@Gd2O3‐PEG aqueous solution. (Reprinted with permission from Zou et al. (2017). Copyright 2017 American Chemical Society). (d) Schematic illustration of trimodal imaging MSN‐probes for tumor draining sentinel lymph nodes (T‐SLNs). MSNs were loaded with Gd3+, 64Cu, and ZW900 (near‐infrared [NIR] dye). (e) Long‐term optical imaging ability and biodistribution of MSN‐probe in vivo. Ex vivo imaging of different organ retrieved from the mouse. (f) MRI of lymph nodes were shown before and after injection of MSN‐probe. Arrow, the accumulation area of particles in lymph node. (g) Positron emission tomography (PET) imaging of tumor‐sentinel lymph node (square dot) and normal‐sentinel lymph node (solid line) after injection of particles for 1 hr and 2 days (upper: cross section, lower: transverse section). (Reprinted with permission from Huang et al. (2012). Copyright 2012 Elsevier)
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Functional mesoporous silica nanoparticles (MSNs) for ultrasound imaging applications. (a) Schematic illustration of the fabrication process of hollow MSN loaded with temperature‐sensitive biocompatible perfluorohexane (PFH) compound as a bubble generator. (b) Typical in vitro ultrasound images before (left column) and after (right column) injection of hollow MSN‐PFH into bovine livers at 70 W for 10 s ultrasound exposure. (Reprinted with permission from Wang et al. (2012). Copyright 2012 Wiley‐VCH). (c) Schematic image of the improvement of ultrasound contrast in exosome‐like silica (ELS)‐labeled stem cells by increasing the echogenicity of the nanoparticles. (d) in vitro echogenicity of the four types of silica nanoparticles. (e) in vivo ultrasound images of mouse after subcutaneously injection of phosphate‐buffered saline (PBS), nonlabeled human mesenchymal stem cells (hMSCs), and ELS‐labeled hMSCs. (Reprinted with permission from Chen et al. (2017). Copyright 2017 the Royal Society of Chemistry)
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Functional mesoporous silica nanoparticles (MSNs) for computed tomography (CT) imaging. (a) Schematic illustration of the synthetic procedure (left) and transmission electron microscope (TEM) image (right) of Au@MSNs loaded with near‐infrared (NIR) dye. CT images of nude mice (b) before and (c) 4 hr after intravenous injection from different views. (Reprinted with permission from Song et al. (2015). Copyright 2015 the American Chemical Society). (d) Illustration of preparation for FePt@MSN@PDA‐Fe3+‐poly(ethylene glycol) (PEG) where FePt nanoparticles and Fe3+ ions function as CT and T1 magnetic resonance imaging (MRI) contrast agent, respectively. (e) The in vivo 3D CT images of mice before injection (left), intravenously injected with saline solution (middle) and intravenously injected with FePt@MSN@PDA‐Fe3+‐PEG. (Reprinted with permission from Chen et al. (2017). Copyright 2017 Wiley‐VCH)
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Functional mesoporous silica nanoparticles (MSNs) for positron emission tomography (PET) applications. (a) Transmission electron microscope (TEM) image (left) and schematic (right) of 64Cu‐NOTA‐MSNs‐PEG‐TRC105 in phosphate‐buffered saline (PBS) solution. (b) Serial coronal PET images of 4T1 tumor‐bearing mice at different time points after intravenous injection of 64Cu‐NOTA‐MSNs‐PEG‐TRC105. Tumors were indicated by yellow arrowheads. (Reprinted with permission from Chen et al. (2013). Copyright 2013 American Chemical Society). (c) TEM image of MSNs and schematic illustration showing the labeling of 89Zr4+ to the deprotonated silanol groups (SiO) from the outer surface and inner mesochannels of MSNs. (d, e) in vivo serial coronal maximum intensity projection PET images of mice at different time points after intravenous injection of (d) 89Zr‐dense silica nanoparticles and (e) 89Zr‐MSNs. (Reprinted with permission from Chen et al. (2015). Copyright 2015 American Chemical Society). (f) The procedure for the in situ synthesis of 18F‐DBCOT‐PEG‐MSNs in a living specimen by a bio‐orthogonal strain‐promoted alkyne‐azide cycloaddition (SPAAC) reaction for the azadibenzocyclooctyne (DBCO)‐poly(ethylene glycol) (PEG)‐MSNs‐pretargeting PET imaging study. Three‐dimensional reconstruction (upper) and transverse section (lower) combined PET‐computed tomography (CT) images of 18F‐labeled azide in a U87 MG tumor‐bearing mouse given only nonpretargeted; (g) or a mouse given DBCO‐PEG‐MSNs 24 hr earlier (pretargeted; (h) recorded at 15, 30, 60, and 120 min after injection of 18F. (Reprinted with permission from Lee et al. (2013). Copyright 2013 Wiley‐VCH)
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Functional mesoporous silica nanoparticles (MSNs) for magnetic resonance imaging (MRI) applications. (a) Schematic illustration of the synthetic procedure for superparamagnetic Fe3O4@MSN core–shell nanoparticles. (b) Transmission electron microscope (TEM) images of uniform Fe3O4@MSNs of 45 nm, 60 nm, and 90 nm. (c) in vivo T2‐weighted MR images (upper row) and color maps (lower row) of T2‐weighted MR images of tumor before and after the Fe3O4@MSNs was intravenously injected into the tail vein of a nude mouse implanted with MCF‐7 human breast cancer cells. A decrease of signal intensity on T2‐weighted MR images was detected at the tumor site (arrows). (Reprinted with permission from Kim et al. (2008). Copyright 2008 Wiley‐VCH). (d) Scanning electron microscope (SEM) image of MSNs‐diethylenetriamine tetraacetic acid (DTTA)‐Gd showing the formation of monodisperse, water‐dispersible nanoparticles. (e) A schematic illustration of the MSNs‐DTTA‐Gd representing the loading Gd3+ ions in hexagonally ordered mesopores of approximately 2.4 nm in diameter via coordination chemistry. (f) T1‐weighted MR images of monocyte cell pellets incubated without MSN‐DTTA‐Gd (left) and with MSN‐DTTA‐Gd for in media (right). (g) Precontrast and postcontrast (2.1 μmol/kg dose) T1‐weighted mouse MR image showing aorta signal enhancement after 15 min injection of MSN‐DTTA‐Gd in DBA/1j mouse. (Reprinted with permission from Taylor et al. (2008). Copyright 2008 the American Chemical Society). (h) Schematic illustration of the synthesis of hollow MnO@MSNs and their application for the labeling of MSCs. (i) TEM image and (j) T1 signal map (left) and plot of 1/T1 vs Mn concentration (right) of HMnO@MSNs suspended in water at 11.7 T. (k) in vivo MRI of mouse brain after transplantation of MSCs labeled with hollow MnO@MSNs. Hyperintense signals (green arrows) were detected in mouse transplanted with HMnO@MSNs‐labeled MSCs. (Reprinted with permission from Kim et al. (2011). Copyright 2011 the American Chemical Society). (l) TEM image (left) and schematic (right) of T2 core (Fe3O4)/T1 nanoparticles (MnO) in MSNs. (m) Axial view of T1‐ and T2‐weighted MR images of MnO/MSNs, Fe3O4@MSNs and Fe3O4/MnO@MSNs representing both high T1 and T2 signals achieved by Fe3O4/MnO@MSNs. (n) In situ T1 − T2 MRI images of mouse brain after unilateral injection of dual‐modal contrast agent (Fe3O4/MnO@MSNs−CD133) into the left ventricular–subventricular zone for the targeting of CD133 positive neural stem cells. The red arrow indicates the injection site. (Reprinted with permission from Peng et al. (2017). Copyright 2017 American Chemical Society)
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Functional mesoporous silica nanoparticles (MSNs) for optical imaging. (a) Transmission electron microscope (TEM) images of a MSN sample and an indocyanine green (ICG) molecule adsorbed to the pores of a MSN sample by electrostatic interactions. (b) Fluorescent imaging intensity of different concentration of free ICG and ICG loaded on the pores of MSN (MSN–ICG) in aqueous solution. (c) Biodistribution of MSN–ICG in an anesthetized rat after intravenous injection for 90 min (upper) and representative fluorescent image of dissected organs from a rat sacrificed after intravenous injection of MSN‐ICG for 3 hr (lower). (Reprinted with permission from Lee et al. (). Copyright 2009 Wiley‐VCH). (d) A scheme for preparation of PEGylated liposome‐coated quantum dots (QDs)/MSNs core–shell nanoparticles. (e) Confocal images of MCF‐7 human breast cancer cells after treatment with PEGylated liposome‐coated QDs/MSNs core–shell nanoparticles. (Reprinted with permission from Pan et al. (2011). Copyright 2011 the Royal Society of Chemistry). (f) TEM images of the carbon dots (CDs)@MSNs. (g) The emission spectra of the CDs@MSNs by excitation with different wavelength. (h) The frozen section of liver and spleen from the mice administrated with CDs@MSNs and CDs after intravenous injection at different interval. (Reprinted with permission from Fu et al. (2015). Copyright 2015 the Royal Society of Chemistry. (i) Schematic illustration of the synthetic procedure for UCNP@MSN core–shell nanocomposites. (j) Confocal images of MCF‐7 human breast cancer cells incubated with NaYF4:Tm/Yb/Gd@MSNs. (k) in vivo upconversion luminescence imaging of a tumor‐bearing mouse after local injection of UCNP@MSNs at the tumor site. (Reprinted with permission from Liu et al. (2012). Copyright 2012 Wiley‐VCH)
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Diagnostic Tools > In Vivo Nanodiagnostics and Imaging
Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

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