Targeted Nanobubbles Carrying Indocyanine Green for Ultrasound, Photoacoustic and Fluorescence Imaging of Prostate Cancer

Yixuan Wang,1 Minmin Lan,2 Daijia Shen,2 Kejing Fang,2 Lianhua Zhu,2 Yu Liu,2 Lan Hao,3 Pan Li3 1The First Clinical College, Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Ultrasound, Southwest Hospital, Army Medical University, Chongqing, People&rs...

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Autores principales:	Wang Y, Lan M, Shen D, Fang K, Zhu L, Liu Y, Hao L, Li P
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	prostate-specific membrane antigen peptide indocyanine green targeted nanobubbles ultrasound molecular imaging photoacoustic imaging Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/755324b9bee840e4b50d56f8e34fe244
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spelling	oai:doaj.org-article:755324b9bee840e4b50d56f8e34fe2442021-12-02T10:00:48ZTargeted Nanobubbles Carrying Indocyanine Green for Ultrasound, Photoacoustic and Fluorescence Imaging of Prostate Cancer1178-2013https://doaj.org/article/755324b9bee840e4b50d56f8e34fe2442020-06-01T00:00:00Zhttps://www.dovepress.com/targeted-nanobubbles-carrying-indocyanine-green-for-ultrasound-photoac-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yixuan Wang,1 Minmin Lan,2 Daijia Shen,2 Kejing Fang,2 Lianhua Zhu,2 Yu Liu,2 Lan Hao,3 Pan Li3 1The First Clinical College, Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Ultrasound, Southwest Hospital, Army Medical University, Chongqing, People’s Republic of China; 3Institute of Ultrasound Imaging, Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Pan LiInstitute of Ultrasound Imaging, Chongqing Medical University, Chongqing, People’s Republic of ChinaEmail lipan@hospital.cqmu.edu.cnObjective: To construct prostate-specific membrane antigen (PSMA)-targeting, indocyanine green (ICG)-loaded nanobubbles (NBs) for multimodal (ultrasound, photoacoustic and fluorescence) imaging of prostate cancer.Methods: The mechanical oscillation method was used to prepare ICG-loaded photoacoustic NBs (ICG NBs). Then, PSMA-binding peptides were connected to the surface of ICG NBs using the biotin–avidin method to make targeted photoacoustic NBs, namely, PSMAP/ICG NBs. Their particle sizes, zeta potentials, and in vitro ultrasound, photoacoustic and fluorescence imaging were examined. Confocal laser scanning microscopy and flow cytometry were used to detect the binding ability of the PSMAP/ICG NBs to PSMA-positive LNCaP cells, C4-2 cells, and PSMA-negative PC-3 cells. The multimodal imaging effects of PSMAP/ICG NBs and ICG NBs were compared in nude mouse tumor xenografts.Results: The particle size of the PSMAP/ICG NBs was approximately 457.7 nm, and the zeta potential was approximately − 23.5 mV. Both confocal laser scanning microscopy and flow cytometry confirmed that the PSMAP/ICG NBs could specifically bind to both LNCaP and C4-2 cells, but they rarely bound to PC-3 cells. The ultrasound, photoacoustic and fluorescence imaging intensities of the PSMAP/ICG NBs in vitro positively correlated with their concentrations. The ultrasound and photoacoustic imaging effects of the PSMAP/ICG NBs in LNCaP and C4-2 tumor xenografts were significantly enhanced compared with those in PC-3 tumor xenografts, which were characterized by a significantly increased duration of ultrasound enhancement and heightened photoacoustic signal intensity (P < 0.05). Fluorescence imaging showed that PSMAP/ICG NBs could accumulate in LNCaP and C4-2 tumor xenografts for a relatively long period.Conclusion: The targeted photoacoustic nanobubbles prepared in this study can specifically bind to PSMA-positive prostate cancer cells and have the ability to enhance ultrasound, photoacoustic and fluorescence imaging of PSMA-positive tumor xenografts. Photoacoustic imaging could visually display the intensity of the red photoacoustic signal in the tumor region, providing a more intuitive imaging modality for targeted molecular imaging. This study presents a potential multimodal contrast agent for the accurate diagnosis and assessment of prostate cancer.Keywords: prostate-specific membrane antigen, peptide, indocyanine green, targeted nanobubbles, ultrasound molecular imaging, photoacoustic imagingWang YLan MShen DFang KZhu LLiu YHao LLi PDove Medical Pressarticleprostate-specific membrane antigenpeptideindocyanine greentargeted nanobubblesultrasound molecular imagingphotoacoustic imagingMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 4289-4309 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	prostate-specific membrane antigen peptide indocyanine green targeted nanobubbles ultrasound molecular imaging photoacoustic imaging Medicine (General) R5-920
spellingShingle	prostate-specific membrane antigen peptide indocyanine green targeted nanobubbles ultrasound molecular imaging photoacoustic imaging Medicine (General) R5-920 Wang Y Lan M Shen D Fang K Zhu L Liu Y Hao L Li P Targeted Nanobubbles Carrying Indocyanine Green for Ultrasound, Photoacoustic and Fluorescence Imaging of Prostate Cancer
description	Yixuan Wang,1 Minmin Lan,2 Daijia Shen,2 Kejing Fang,2 Lianhua Zhu,2 Yu Liu,2 Lan Hao,3 Pan Li3 1The First Clinical College, Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Ultrasound, Southwest Hospital, Army Medical University, Chongqing, People’s Republic of China; 3Institute of Ultrasound Imaging, Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Pan LiInstitute of Ultrasound Imaging, Chongqing Medical University, Chongqing, People’s Republic of ChinaEmail lipan@hospital.cqmu.edu.cnObjective: To construct prostate-specific membrane antigen (PSMA)-targeting, indocyanine green (ICG)-loaded nanobubbles (NBs) for multimodal (ultrasound, photoacoustic and fluorescence) imaging of prostate cancer.Methods: The mechanical oscillation method was used to prepare ICG-loaded photoacoustic NBs (ICG NBs). Then, PSMA-binding peptides were connected to the surface of ICG NBs using the biotin–avidin method to make targeted photoacoustic NBs, namely, PSMAP/ICG NBs. Their particle sizes, zeta potentials, and in vitro ultrasound, photoacoustic and fluorescence imaging were examined. Confocal laser scanning microscopy and flow cytometry were used to detect the binding ability of the PSMAP/ICG NBs to PSMA-positive LNCaP cells, C4-2 cells, and PSMA-negative PC-3 cells. The multimodal imaging effects of PSMAP/ICG NBs and ICG NBs were compared in nude mouse tumor xenografts.Results: The particle size of the PSMAP/ICG NBs was approximately 457.7 nm, and the zeta potential was approximately − 23.5 mV. Both confocal laser scanning microscopy and flow cytometry confirmed that the PSMAP/ICG NBs could specifically bind to both LNCaP and C4-2 cells, but they rarely bound to PC-3 cells. The ultrasound, photoacoustic and fluorescence imaging intensities of the PSMAP/ICG NBs in vitro positively correlated with their concentrations. The ultrasound and photoacoustic imaging effects of the PSMAP/ICG NBs in LNCaP and C4-2 tumor xenografts were significantly enhanced compared with those in PC-3 tumor xenografts, which were characterized by a significantly increased duration of ultrasound enhancement and heightened photoacoustic signal intensity (P < 0.05). Fluorescence imaging showed that PSMAP/ICG NBs could accumulate in LNCaP and C4-2 tumor xenografts for a relatively long period.Conclusion: The targeted photoacoustic nanobubbles prepared in this study can specifically bind to PSMA-positive prostate cancer cells and have the ability to enhance ultrasound, photoacoustic and fluorescence imaging of PSMA-positive tumor xenografts. Photoacoustic imaging could visually display the intensity of the red photoacoustic signal in the tumor region, providing a more intuitive imaging modality for targeted molecular imaging. This study presents a potential multimodal contrast agent for the accurate diagnosis and assessment of prostate cancer.Keywords: prostate-specific membrane antigen, peptide, indocyanine green, targeted nanobubbles, ultrasound molecular imaging, photoacoustic imaging
format	article
author	Wang Y Lan M Shen D Fang K Zhu L Liu Y Hao L Li P
author_facet	Wang Y Lan M Shen D Fang K Zhu L Liu Y Hao L Li P
author_sort	Wang Y
title	Targeted Nanobubbles Carrying Indocyanine Green for Ultrasound, Photoacoustic and Fluorescence Imaging of Prostate Cancer
title_short	Targeted Nanobubbles Carrying Indocyanine Green for Ultrasound, Photoacoustic and Fluorescence Imaging of Prostate Cancer
title_full	Targeted Nanobubbles Carrying Indocyanine Green for Ultrasound, Photoacoustic and Fluorescence Imaging of Prostate Cancer
title_fullStr	Targeted Nanobubbles Carrying Indocyanine Green for Ultrasound, Photoacoustic and Fluorescence Imaging of Prostate Cancer
title_full_unstemmed	Targeted Nanobubbles Carrying Indocyanine Green for Ultrasound, Photoacoustic and Fluorescence Imaging of Prostate Cancer
title_sort	targeted nanobubbles carrying indocyanine green for ultrasound, photoacoustic and fluorescence imaging of prostate cancer
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/755324b9bee840e4b50d56f8e34fe244
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Targeted Nanobubbles Carrying Indocyanine Green for Ultrasound, Photoacoustic and Fluorescence Imaging of Prostate Cancer

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