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Nano Research 2020, 13(4): 1100-1110 https://doi.org/10.1007/s12274-020-2752-6
Research Article | Issue | Published: 14 April 2020

Temperature-sensitive polymeric nanogels encapsulating with β-cyclodextrin and ICG complex for high-resolution deep-tissue ultrasound-switchable fluorescence imaging

Show Author's Information Ruilin Liu1,2,§,  Tingfeng Yao1,2,§,  Yang Liu1,2,  Shuai Yu1,2,  Liqin Ren1,2,  Yi Hong2,3,  Kytai T. Nguyen2,3,  Baohong Yuan1,2( )
Ultrasound and Optical Imaging Laboratory, Department of Bioengineering, the University of Texas at Arlington, Arlington, TX 76019, USA
Joint Biomedical Engineering Program, the University of Texas at Arlington and the University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Department of Bioengineering, the University of Texas at Arlington, Arlington, TX 76019, USA

§ Ruilin Liu and Tingfeng Yao contributed equally to this work.

Keywords:
in vivo imaging, deep tissue imaging, high-resolution, ultrasound-switchable NIR fluorescence imaging
Topics:
BiocompatibilityHistologyInfrared devices MammalsMedical imagingNanoparticlesNanostructured materialsProbesTumors
Cite this article:
Liu R, Yao T, Liu Y, et al. Temperature-sensitive polymeric nanogels encapsulating with β-cyclodextrin and ICG complex for high-resolution deep-tissue ultrasound-switchable fluorescence imaging. Nano Research, 2020, 13(4): 1100-1110. https://doi.org/10.1007/s12274-020-2752-6
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Abstract Full text Electronic supplementary material About this article

One of the thorny problems currently impeding the applications of the fluorescence imaging technique is the poor spatial resolution in deep tissue. Ultrasound-switchable fluorescence (USF) imaging is a novel imaging tool that has recently been explored to possibly surmount the above-mentioned bottleneck. Herein, a β-cyclodextrin/indocyanine green (ICG) complex-encapsulated poly(N-isopropylacrylamide) (PNIPAM) nanogel was synthesized and studied for ex vivo/in vivo deep tissue/high-resolution near infrared USF (NIR-USF) imaging. To be specific, our results revealed that the average diameter of the as-prepared nanogels was significantly decreased to ~ 32 nm from ~ 335 nm compared to the reported ICG-PNIPAM nanoparticles. Additionally, the excitation/ emission characteristics of the ICG itself in present nanogels were almost completely retained, and the resultant nanogel exhibited high physiological stability and positive biocompatibility. In particular, the signal-to-noise ratio of the USF image for the PNIPAM/ β-cyclodextrin/ICG nanogel (33.01 ± 2.42 dB) was prominently higher than that of the ICG-PNIPAM nanoparticles (18.73 ± 0.33 dB) in 1.5-cm-thick chicken breast tissues. The NIR-USF imaging in 3.5-cm-thick chicken breast tissues was achieved using this new probe. The ex vivo NIR-USF imaging of the mouse liver was also successfully obtained. Animal experiments showed that the present nanogels were able to be effectively accumulated into U87 tumor-bearing mice via enhanced permeability and retention effects, and the high-resolution NIR-USF imaging of in vivo tumor was efficiently acquired. The metabolism and in vivo biodistribution of the nanogels were evaluated. Overall, the results suggest that the current nanogel is a highly promising NIR-USF probe for deep tissue and high-resolution USF imaging.


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Abstract
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Electronic supplementary material
About this article

Temperature-sensitive polymeric nanogels encapsulating with β-cyclodextrin and ICG complex for high-resolution deep-tissue ultrasound-switchable fluorescence imaging

Show Author's information Ruilin Liu1,2,§, Tingfeng Yao1,2,§, Yang Liu1,2, Shuai Yu1,2, Liqin Ren1,2, Yi Hong2,3, Kytai T. Nguyen2,3, Baohong Yuan1,2( )
Ultrasound and Optical Imaging Laboratory, Department of Bioengineering, the University of Texas at Arlington, Arlington, TX 76019, USA
Joint Biomedical Engineering Program, the University of Texas at Arlington and the University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Department of Bioengineering, the University of Texas at Arlington, Arlington, TX 76019, USA

§ Ruilin Liu and Tingfeng Yao contributed equally to this work.

Abstract

One of the thorny problems currently impeding the applications of the fluorescence imaging technique is the poor spatial resolution in deep tissue. Ultrasound-switchable fluorescence (USF) imaging is a novel imaging tool that has recently been explored to possibly surmount the above-mentioned bottleneck. Herein, a β-cyclodextrin/indocyanine green (ICG) complex-encapsulated poly(N-isopropylacrylamide) (PNIPAM) nanogel was synthesized and studied for ex vivo/in vivo deep tissue/high-resolution near infrared USF (NIR-USF) imaging. To be specific, our results revealed that the average diameter of the as-prepared nanogels was significantly decreased to ~ 32 nm from ~ 335 nm compared to the reported ICG-PNIPAM nanoparticles. Additionally, the excitation/ emission characteristics of the ICG itself in present nanogels were almost completely retained, and the resultant nanogel exhibited high physiological stability and positive biocompatibility. In particular, the signal-to-noise ratio of the USF image for the PNIPAM/ β-cyclodextrin/ICG nanogel (33.01 ± 2.42 dB) was prominently higher than that of the ICG-PNIPAM nanoparticles (18.73 ± 0.33 dB) in 1.5-cm-thick chicken breast tissues. The NIR-USF imaging in 3.5-cm-thick chicken breast tissues was achieved using this new probe. The ex vivo NIR-USF imaging of the mouse liver was also successfully obtained. Animal experiments showed that the present nanogels were able to be effectively accumulated into U87 tumor-bearing mice via enhanced permeability and retention effects, and the high-resolution NIR-USF imaging of in vivo tumor was efficiently acquired. The metabolism and in vivo biodistribution of the nanogels were evaluated. Overall, the results suggest that the current nanogel is a highly promising NIR-USF probe for deep tissue and high-resolution USF imaging.

Keywords: in vivo imaging, deep tissue imaging, high-resolution, ultrasound-switchable NIR fluorescence imaging

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Acknowledgements

Publication history

Received: 03 January 2020
Revised: 06 March 2020
Accepted: 07 March 2020
Published: 14 April 2020
Issue date: April 2020

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020

Acknowledgements

This work was supported in part by funding from the CPRIT RP170564 (Baohong Yuan) and the NSF CBET-1253199 (Baohong Yuan).

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