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Near-infrared fluorescence imaging has emerged as a noninvasive, inexpensive, and ionizing-radiation-free monitoring tool for assessing tumor growth and treatment efficacy. In particular, ultrasound switchable fluorescence (USF) imaging has been explored with improved imaging sensitivity and spatial resolution in centimeter-deep tissues. This study achieved the size control of polymer-based and indocyanine green (ICG) encapsulated USF contrast agents, capable of accumulating in the tumor after intravenous injections. These nanoprobes varied in size from 58 to 321 nm. The bioimaging profiles demonstrated that the proposed nanoparticles can efficiently eliminate the background light from normal tissue and show a tumor-specific fluorescence enhancement in the BxPC-3 tumor-bearing mice models possibly via the enhanced permeability and retention effect. In vivo tumor USF imaging further demonstrated that these nanoprobes can effectively be switched “ON” with enhanced fluorescence in response to a focused ultrasound stimulation in the tumor microenvironment, contributing to the high-resolution USF images. Therefore, our findings suggest that ICG-encapsulated nanoparticles are good candidates for USF imaging of tumors in live animals, indicating their great potential in optical tumor imaging in deep tissue.


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In vivo tumor ultrasound-switchable fluorescence imaging via intravenous injections of size-controlled thermosensitive nanoparticles

Show Author's information Liqin Ren1,2,§Yang Liu1,2,§Tingfeng Yao1,2Kytai T. Nguyen2,3Baohong 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

§ Liqin Ren and Yang Liu contributed equally to this work.

Abstract

Near-infrared fluorescence imaging has emerged as a noninvasive, inexpensive, and ionizing-radiation-free monitoring tool for assessing tumor growth and treatment efficacy. In particular, ultrasound switchable fluorescence (USF) imaging has been explored with improved imaging sensitivity and spatial resolution in centimeter-deep tissues. This study achieved the size control of polymer-based and indocyanine green (ICG) encapsulated USF contrast agents, capable of accumulating in the tumor after intravenous injections. These nanoprobes varied in size from 58 to 321 nm. The bioimaging profiles demonstrated that the proposed nanoparticles can efficiently eliminate the background light from normal tissue and show a tumor-specific fluorescence enhancement in the BxPC-3 tumor-bearing mice models possibly via the enhanced permeability and retention effect. In vivo tumor USF imaging further demonstrated that these nanoprobes can effectively be switched “ON” with enhanced fluorescence in response to a focused ultrasound stimulation in the tumor microenvironment, contributing to the high-resolution USF images. Therefore, our findings suggest that ICG-encapsulated nanoparticles are good candidates for USF imaging of tumors in live animals, indicating their great potential in optical tumor imaging in deep tissue.

Keywords: high resolution, in vivo tumor imaging, deep tissue near-infrared (NIR) imaging, ultrasound-switchable fluorescence imaging, indocyanine green (ICG)

References(31)

[1]

Bray, F.; Laversanne, M.; Weiderpass, E.; Soerjomataram, I. The ever-increasing importance of cancer as a leading cause of premature death worldwide. Cancer 2021, 127, 3029–3030.

[2]

Siegel, R. L.; Miller, K. D.; Fuchs, H. E.; Jemal, A. Cancer statistics, 2022. CA Cancer J. Clin. 2022, 72, 7–33.

[3]

Kosaka, N.; Ogawa, M.; Choyke, P. L.; Kobayashi, H. Clinical implications of near-infrared fluorescence imaging in cancer. Future Oncol. 2009, 5, 1501–1511.

[4]

Namikawa, T.; Sato, T.; Hanazaki, K. Recent advances in near-infrared fluorescence-guided imaging surgery using indocyanine green. Surg. Today 2015, 45, 1467–1474.

[5]

Ohnishi, S.; Lomnes, S. J.; Laurence, R. G.; Gogbashian, A.; Mariani, G.; Frangioni, J. V. Organic alternatives to quantum dots for intraoperative near-infrared fluorescent sentinel lymph node mapping. Mol. Imaging 2005, 4, 172–181.

[6]

Schaafsma, B. E.; Mieog, J. S. D.; Hutteman, M.; van der Vorst, J. R.; Kuppen, P. J. K.; Löwik, C. W. G. M.; Frangioni, J. V.; van de Velde, C. J. H.; Vahrmeijer, A. L. The clinical use of indocyanine green as a near-infrared fluorescent contrast agent for image-guided oncologic surgery. J. Surg. Oncol. 2011, 104, 323–332.

[7]

Liu, R. L.; Yao, T. F.; Liu, Y.; Yu, S.; Ren, L. Q.; Hong, Y.; Nguyen, K. T.; Yuan, B. H. Temperature-sensitive polymeric nanogels encapsulating with β-cyclodextrin and ICG complex for high-resolution deep-tissue ultrasound-switchable fluorescence imaging. Nano Res. 2020, 13, 1100–1110.

[8]

Yao, T. F.; Liu, Y.; Ren, L. Q.; Yuan, B. H. Improving sensitivity and imaging depth of ultrasound-switchable fluorescence via an EMCCD-gain-controlled system and a liposome-based contrast agent. Quant. Imaging Med. Surg. 2021, 11, 957–968.

[9]

Yu, S.; Cheng, B. B.; Yao, T. F.; Xu, C. C.; Nguyen, K. T.; Hong, Y.; Yuan, B. H. New generation ICG-based contrast agents for ultrasound-switchable fluorescence imaging. Sci. Rep. 2016, 6, 35942.

[10]

Yu, S.; Yao, T. F.; Liu, Y.; Yuan, B. H. In vivo ultrasound-switchable fluorescence imaging using a camera-based system. Biomed. Opt. Express 2020, 11, 1517–1538.

[11]

Yao, T. F.; Yu, S.; Liu, Y.; Yuan, B. H. In vivo ultrasound-switchable fluorescence imaging. Sci. Rep. 2019, 9, 9855.

[12]

Liu, Y.; Yao, T. F.; Cai, W. B.; Yu, S.; Hong, Y.; Nguyen, K. T.; Yuan, B. H. A biocompatible and near-infrared liposome for in vivo ultrasound-switchable fluorescence imaging. Adv. Healthc. Mater. 2020, 9, 1901457.

[13]

Cheng, B. B.; Bandi, V.; Wei, M. Y.; Pei, Y. B.; D’Souza, F.; Nguyen, K. T.; Hong, Y.; Yuan, B. H. High-resolution ultrasound-switchable fluorescence imaging in centimeter-deep tissue phantoms with high signal-to-noise ratio and high sensitivity via novel contrast agents. PLoS One 2016, 11, e0165963.

[14]

Andersson, M.; Maunu, S. L. Structural studies of poly (N-isopropylacrylamide) microgels: Effect of SDS surfactant concentration in the microgel synthesis. J. Polym. Sci. Part B Polym. Phys. 2006, 44, 3305–3314.

[15]

Danaei, M.; Dehghankhold, M.; Ataei, S.; Hasanzadeh Davarani, F.; Javanmard, R.; Dokhani, A.; Khorasani, S.; Mozafari, M. R. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics 2018, 10, 57.

[16]

Acharya, S.; Sahoo, S. K. PLGA nanoparticles containing various anticancer agents and tumour delivery by EPR effect. Adv. Drug Deliv. Rev. 2011, 63, 170–183.

[17]

Fröhlich, E. The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles. Int. J. Nanomedicine 2012, 67, 5577–5591.

[18]

Gehling, A. M.; Kuszpit, K.; Bailey, E. J.; Allen-Worthington, K. H.; Fetterer, D. P.; Rico, P. J.; Bocan, T. M.; Hofer, C. C. Evaluation of volume of intramuscular injection into the caudal thigh muscles of female and male BALB/c mice (Mus musculus). J. Am. Assoc. Lab. Anim. Sci. 2018, 57, 35–43.

[19]

Yu, M. X.; Zheng, J. Clearance pathways and tumor targeting of imaging nanoparticles. ACS Nano 2015, 9, 6655–6674.

[20]

Gustafson, H. H.; Holt-Casper, D.; Grainger, D. W.; Ghandehari, H. Nanoparticle uptake: The phagocyte problem. Nano Today 2015, 10, 487–510.

[21]

de Wet, C.; Moss, J. Metabolic functions of the lung. Anesthesiol. Clin. North Am. 1998, 16, 181–199.

[22]

Anselmo, A. C.; Gupta, V.; Zern, B. J.; Pan, D.; Zakrewsky, M.; Muzykantov, V.; Mitragotri, S. Delivering nanoparticles to lungs while avoiding liver and spleen through adsorption on red blood cells. ACS Nano 2013, 7, 11129–11137.

[23]

Izci, M.; Maksoudian, C.; Manshian, B. B.; Soenen, S. J. The use of alternative strategies for enhanced nanoparticle delivery to solid tumors. Chem. Rev. 2021, 121, 1746–1803.

[24]

Longmire, M.; Choyke, P. L.; Kobayashi, H. Clearance properties of nano-sized particles and molecules as imaging agents: Considerations and caveats. Nanomedicine 2008, 3, 703–717.

[25]

Sykes, E. A.; Dai, Q.; Sarsons, C. D.; Chen, J.; Rocheleau, J. V.; Hwang, D. M.; Zheng, G.; Cramb, D. T.; Rinker, K. D.; Chan, W. C. W. Tailoring nanoparticle designs to target cancer based on tumor pathophysiology. Proc. Natl. Acad. Sci. USA 2016, 113, E1142–E1151.

[26]

Fang, J.; Islam, W.; Maeda, H. Exploiting the dynamics of the EPR effect and strategies to improve the therapeutic effects of nanomedicines by using EPR effect enhancers. Adv. Drug Deliv. Rev. 2020, 157, 142–160.

[27]

Campbell, R. B.; Fukumura, D.; Brown, E. B.; Mazzola, L. M.; Izumi, Y.; Jain, R. K.; Torchilin, V. P.; Munn, L. L. Cationic charge determines the distribution of liposomes between the vascular and extravascular compartments of tumors. Cancer Res. 2002, 62, 6831–6836.

[28]

Yao, T. F.; Yu, S.; Liu, Y.; Yuan, B. H. Ultrasound-switchable fluorescence imaging via an EMCCD camera and a Z-scan method. IEEE J. Sel. Top. Quantum Electron. 2019, 25, 1–8.

[29]

Luo, H. M.; England, C. G.; Goel, S.; Graves, S. A.; Ai, F. R.; Liu, B.; Theuer, C. P.; Wong, H. C.; Nickles, R. J.; Cai, W. B. ImmunoPET and near-infrared fluorescence imaging of pancreatic cancer with a dual-labeled bispecific antibody fragment. Mol. Pharm. 2017, 14, 1646–1655.

[30]

Hausner, S. H.; Abbey, C. K.; Bold, R. J.; Gagnon, M. K.; Marik, J.; Marshall, J. F.; Stanecki, C. E.; Sutcliffe, J. L. Targeted in vivo imaging of integrin αvβ6 with an improved radiotracer and its relevance in a pancreatic tumor model. Cancer Res. 2009, 69, 5843–5850.

[31]

Ren, S.; Song, L. N.; Tian, Y.; Zhu, L.; Guo, K.; Zhang, H. F.; Wang, Z. Q. Emodin-conjugated PEGylation of Fe3O4 nanoparticles for FI/MRI dual-modal imaging and therapy in pancreatic cancer. Int. J. Nanomedicine 2021, 16, 7463–7478.

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Publication history
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Acknowledgements

Publication history

Received: 13 May 2022
Revised: 13 May 2022
Accepted: 01 August 2022
Published: 21 September 2022
Issue date: January 2023

Copyright

© Tsinghua University Press 2022

Acknowledgements

Acknowledgements

This work was supported in part by funding from the National Institute of Biomedical Imaging and Bioengineering (No. 1R15EB030809-01), the Research Enhancement Program (No. 270089), and the Cancer Prevention & Research Institute of Texas (Nos. RP170564 and RP210206).

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