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Upconversion nanoparticles: a versatile solution to multiscale biological imaging.

Wu X, Chen G, Shen J, Li Z, Zhang Y, Han G - Bioconjug. Chem. (2014)

Bottom Line: Lanthanide-doped photon upconverting nanomaterials are emerging as a new class of imaging contrast agents, providing numerous unprecedented possibilities in the realm of biomedical imaging.Because of their ability to convert long-wavelength near-infrared excitation radiation into shorter-wavelength emissions, these nanomaterials are able to produce assets of low imaging background, large anti-Stokes shift, as well as high optical penetration depth of light for deep tissue optical imaging or light-activated drug release and therapy.The aim of this review is to line up some issues associated with conventional fluorescent probes, and to address the recent advances of upconverting nanoparticles (UCNPs) as a solution to multiscale biological imaging applications.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School , Worcester, Massachusetts 01605, United States.

ABSTRACT
Lanthanide-doped photon upconverting nanomaterials are emerging as a new class of imaging contrast agents, providing numerous unprecedented possibilities in the realm of biomedical imaging. Because of their ability to convert long-wavelength near-infrared excitation radiation into shorter-wavelength emissions, these nanomaterials are able to produce assets of low imaging background, large anti-Stokes shift, as well as high optical penetration depth of light for deep tissue optical imaging or light-activated drug release and therapy. The aim of this review is to line up some issues associated with conventional fluorescent probes, and to address the recent advances of upconverting nanoparticles (UCNPs) as a solution to multiscale biological imaging applications.

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(top) left:the tissue depth of NIR and visible light. right: (a)UCPL bright-field image of a cuvette filled with a suspension of thecore/shell nanoparticles, (b) bright-field image of a cuvette coveredwith pork tissue with a quarter coin stood aside showing its thickness,(c) merged UCPL/bright-field image of the cuvette covered with porktissue, and (d) bright-field image of the pork tissue (side view).The inset in (c) shows the spectra obtained from the circled areas.(bottom) Polyethylenimine-coated NIRin-NIRout R-(NaYbF4:0.5%Tm3t)/CaF2 core/shell nanoparticlesfor imaging a synthetic periosteal mesh implanted around a rat femur.(a) UCNPs were loaded on a 7-mm-wide sulfated polymer mesh and wrappedaround the mid shaft of a rat femur. Scale bar: 500 μm. (b)Bright-field image of the rat hind leg after closing muscle/skin bysuture (left) and PL image (right) of the deeply embedded UCNP-stainedsynthetic mesh wrapped around the rat femur. Scale bar: 2 cm. (Reprintedwith permission from ref (34). Copyright 2012 American Chemical Society.)
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fig5: (top) left:the tissue depth of NIR and visible light. right: (a)UCPL bright-field image of a cuvette filled with a suspension of thecore/shell nanoparticles, (b) bright-field image of a cuvette coveredwith pork tissue with a quarter coin stood aside showing its thickness,(c) merged UCPL/bright-field image of the cuvette covered with porktissue, and (d) bright-field image of the pork tissue (side view).The inset in (c) shows the spectra obtained from the circled areas.(bottom) Polyethylenimine-coated NIRin-NIRout R-(NaYbF4:0.5%Tm3t)/CaF2 core/shell nanoparticlesfor imaging a synthetic periosteal mesh implanted around a rat femur.(a) UCNPs were loaded on a 7-mm-wide sulfated polymer mesh and wrappedaround the mid shaft of a rat femur. Scale bar: 500 μm. (b)Bright-field image of the rat hind leg after closing muscle/skin bysuture (left) and PL image (right) of the deeply embedded UCNP-stainedsynthetic mesh wrapped around the rat femur. Scale bar: 2 cm. (Reprintedwith permission from ref (34). Copyright 2012 American Chemical Society.)

Mentions: Compared tovisible UC emission, the NIR UC emission are more interesting in deeptissue imaging, as both excitation and emission wavelengths fall withinthe biological NIR optical transmission window (700–1000 nm).High-contrast deep tissue optical imaging is allowed using NIRin-NIRout UCNPs, as biological tissue will showmuch lower NIR light attenuation and scattering effects, and autofluorescence is absent when collecting the NIR UC emission. Prasadand co-workers first reported high-contrast in vitro and in vivo bioimagingusing NIRin-NIRout NaYF4:Yb3+/Tm3+ UCNPs.36 In order toimprove the UCNPs’ efficiency, the same group by Prasad andco-workers established a novel strategy that not only results in an8-fold enhancement of the quantum yield, but also increases the extinctioncoefficient of every nanoparticle 5 times by elevating the concentrationof the sensitizer Yb3+.37 In2013, Yan et al. reported on the use of biocompatible material ofCaF2 to encapsulate UCNPs cores, displaying emissions 4–5times stronger than the one coated with a traditional NaYF4 inert shell. Using the same strategy, Han et al. developed NaYbF4:Tm3+/CaF2 UCNPs and used for whole-bodymice imaging. An imaging depth as high as ∼3.2 cm was demonstratedusing biological tissue (pork tissue) as a model. Moreover, high-contrastUC imaging of deep tissues was demonstrated by using a nanoparticle-loadedsynthetic fibrous mesh wrapped around rat femoral bone; 7 days afterthe UCNP-loaded mesh was implanted, the operated hind leg was imaged(Figure 5).38


Upconversion nanoparticles: a versatile solution to multiscale biological imaging.

Wu X, Chen G, Shen J, Li Z, Zhang Y, Han G - Bioconjug. Chem. (2014)

(top) left:the tissue depth of NIR and visible light. right: (a)UCPL bright-field image of a cuvette filled with a suspension of thecore/shell nanoparticles, (b) bright-field image of a cuvette coveredwith pork tissue with a quarter coin stood aside showing its thickness,(c) merged UCPL/bright-field image of the cuvette covered with porktissue, and (d) bright-field image of the pork tissue (side view).The inset in (c) shows the spectra obtained from the circled areas.(bottom) Polyethylenimine-coated NIRin-NIRout R-(NaYbF4:0.5%Tm3t)/CaF2 core/shell nanoparticlesfor imaging a synthetic periosteal mesh implanted around a rat femur.(a) UCNPs were loaded on a 7-mm-wide sulfated polymer mesh and wrappedaround the mid shaft of a rat femur. Scale bar: 500 μm. (b)Bright-field image of the rat hind leg after closing muscle/skin bysuture (left) and PL image (right) of the deeply embedded UCNP-stainedsynthetic mesh wrapped around the rat femur. Scale bar: 2 cm. (Reprintedwith permission from ref (34). Copyright 2012 American Chemical Society.)
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fig5: (top) left:the tissue depth of NIR and visible light. right: (a)UCPL bright-field image of a cuvette filled with a suspension of thecore/shell nanoparticles, (b) bright-field image of a cuvette coveredwith pork tissue with a quarter coin stood aside showing its thickness,(c) merged UCPL/bright-field image of the cuvette covered with porktissue, and (d) bright-field image of the pork tissue (side view).The inset in (c) shows the spectra obtained from the circled areas.(bottom) Polyethylenimine-coated NIRin-NIRout R-(NaYbF4:0.5%Tm3t)/CaF2 core/shell nanoparticlesfor imaging a synthetic periosteal mesh implanted around a rat femur.(a) UCNPs were loaded on a 7-mm-wide sulfated polymer mesh and wrappedaround the mid shaft of a rat femur. Scale bar: 500 μm. (b)Bright-field image of the rat hind leg after closing muscle/skin bysuture (left) and PL image (right) of the deeply embedded UCNP-stainedsynthetic mesh wrapped around the rat femur. Scale bar: 2 cm. (Reprintedwith permission from ref (34). Copyright 2012 American Chemical Society.)
Mentions: Compared tovisible UC emission, the NIR UC emission are more interesting in deeptissue imaging, as both excitation and emission wavelengths fall withinthe biological NIR optical transmission window (700–1000 nm).High-contrast deep tissue optical imaging is allowed using NIRin-NIRout UCNPs, as biological tissue will showmuch lower NIR light attenuation and scattering effects, and autofluorescence is absent when collecting the NIR UC emission. Prasadand co-workers first reported high-contrast in vitro and in vivo bioimagingusing NIRin-NIRout NaYF4:Yb3+/Tm3+ UCNPs.36 In order toimprove the UCNPs’ efficiency, the same group by Prasad andco-workers established a novel strategy that not only results in an8-fold enhancement of the quantum yield, but also increases the extinctioncoefficient of every nanoparticle 5 times by elevating the concentrationof the sensitizer Yb3+.37 In2013, Yan et al. reported on the use of biocompatible material ofCaF2 to encapsulate UCNPs cores, displaying emissions 4–5times stronger than the one coated with a traditional NaYF4 inert shell. Using the same strategy, Han et al. developed NaYbF4:Tm3+/CaF2 UCNPs and used for whole-bodymice imaging. An imaging depth as high as ∼3.2 cm was demonstratedusing biological tissue (pork tissue) as a model. Moreover, high-contrastUC imaging of deep tissues was demonstrated by using a nanoparticle-loadedsynthetic fibrous mesh wrapped around rat femoral bone; 7 days afterthe UCNP-loaded mesh was implanted, the operated hind leg was imaged(Figure 5).38

Bottom Line: Lanthanide-doped photon upconverting nanomaterials are emerging as a new class of imaging contrast agents, providing numerous unprecedented possibilities in the realm of biomedical imaging.Because of their ability to convert long-wavelength near-infrared excitation radiation into shorter-wavelength emissions, these nanomaterials are able to produce assets of low imaging background, large anti-Stokes shift, as well as high optical penetration depth of light for deep tissue optical imaging or light-activated drug release and therapy.The aim of this review is to line up some issues associated with conventional fluorescent probes, and to address the recent advances of upconverting nanoparticles (UCNPs) as a solution to multiscale biological imaging applications.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School , Worcester, Massachusetts 01605, United States.

ABSTRACT
Lanthanide-doped photon upconverting nanomaterials are emerging as a new class of imaging contrast agents, providing numerous unprecedented possibilities in the realm of biomedical imaging. Because of their ability to convert long-wavelength near-infrared excitation radiation into shorter-wavelength emissions, these nanomaterials are able to produce assets of low imaging background, large anti-Stokes shift, as well as high optical penetration depth of light for deep tissue optical imaging or light-activated drug release and therapy. The aim of this review is to line up some issues associated with conventional fluorescent probes, and to address the recent advances of upconverting nanoparticles (UCNPs) as a solution to multiscale biological imaging applications.

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