Diagnosis of prostate cancer using anti-PSMA aptamer A10-3.2-oriented lipid nanobubbles

Xiaozhou Fan,1 Yanli Guo,1 Luofu Wang,2 Xingyu Xiong,1 Lianhua Zhu,1 Kejing Fang1 1Department of Ultrasound, Southwest Hospital, Third Military Medical University, Chongqing, People’s Republic of China; 2Department of Urology, Daping Hospital, Institute of Surgery Research, Third Military...

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Autores principales:	Fan X, Guo Y, Wang L, Xiong X, Zhu L, Fang K
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	molecular imaging contrast-enhanced ultrasound aptamer prostate specific membrane antigen targeted imaging Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/58c0086336ea4306b32ec63cd2159533
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spelling	oai:doaj.org-article:58c0086336ea4306b32ec63cd21595332021-12-02T01:32:33ZDiagnosis of prostate cancer using anti-PSMA aptamer A10-3.2-oriented lipid nanobubbles1178-2013https://doaj.org/article/58c0086336ea4306b32ec63cd21595332016-08-01T00:00:00Zhttps://www.dovepress.com/diagnosis-of-prostate-cancer-using-anti-psma-aptamer-a10-32-oriented-l-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xiaozhou Fan,1 Yanli Guo,1 Luofu Wang,2 Xingyu Xiong,1 Lianhua Zhu,1 Kejing Fang1 1Department of Ultrasound, Southwest Hospital, Third Military Medical University, Chongqing, People’s Republic of China; 2Department of Urology, Daping Hospital, Institute of Surgery Research, Third Military Medical University, Chongqing, People’s Republic of China Abstract: In this study, the lipid targeted nanobubble carrying the A10-3.2 aptamer against prostate specific membrane antigen was fabricated, and its effect in the ultrasound imaging of prostate cancer was investigated. Materials including 2-dipalmitoyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoyl-sn-glycero-3-phosphatidic acid, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine, 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol, carboxyl-modified 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, and polyethyleneglycol-2000 were for mechanical oscillation, and nanobubbles were obtained through the centrifugal flotation method. After mice were injected with nanobubbles, abdominal color Doppler blood flow imaging significantly improved. Through left ventricular perfusion with normal saline to empty the circulating nanobubbles, nanobubbles still existed in tumor tissue sections, which demonstrated that nanobubbles could enter tissue spaces via the permeability and retention effect. Fluorinated A10-3.2 aptamers obtained by chemical synthesis had good specificity for PSMA-positive cells, and were linked with carboxyl-modified 1,2-distearoyl-sn-glycero-3-phosphoethanolamine lipid molecules from the outer shell of nanobubbles via amide reaction to construct targeted nanobubbles. Gel electrophoresis and immunofluorescence confirmed that targeted nanobubbles were fabricated successfully. Next, targeted nanobubbles could bind with PSMA-positive cells (C4-2 cells), while not with PSMA-negative cells (PC-3 cells), using in vitro binding experiments and flow cytometry at the cellular level. Finally, C4-2 and PC-3 xenografts in mice were used to observe changes in parameters of targeted and non-targeted nanobubbles in the contrast-enhanced ultrasound mode, and the distribution of Cy5.5-labeled targeted nanobubbles in fluorescent imaging of live small animals. Comparison of ultrasound indicators between targeted and non-targeted nanobubbles in C4-2 xenografts showed that they had similar peak times (P>0.05), while the peak intensity, half time of peak intensity, and area under the curve of ½ peak intensity were significantly different (P<0.05). In PC-3 xenografts, there were no differences in these four indicators. Fluorescent imaging indicated that targeted nanobubbles had an aggregation ability in C4-2 xenograft tumors. In conclusion, targeted nanobubbles carrying the anti-PSMA A10-3.2 aptamer have a targeted imaging effect in prostate cancer. Keywords: molecular imaging, contrast-enhanced ultrasound, aptamer, prostate specific membrane antigen, targeted imagingFan XGuo YWang LXiong XZhu LFang KDove Medical Pressarticlemolecular imagingcontrast-enhanced ultrasoundaptamerprostate specific membrane antigentargeted imagingMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 11, Pp 3939-3950 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	molecular imaging contrast-enhanced ultrasound aptamer prostate specific membrane antigen targeted imaging Medicine (General) R5-920
spellingShingle	molecular imaging contrast-enhanced ultrasound aptamer prostate specific membrane antigen targeted imaging Medicine (General) R5-920 Fan X Guo Y Wang L Xiong X Zhu L Fang K Diagnosis of prostate cancer using anti-PSMA aptamer A10-3.2-oriented lipid nanobubbles
description	Xiaozhou Fan,1 Yanli Guo,1 Luofu Wang,2 Xingyu Xiong,1 Lianhua Zhu,1 Kejing Fang1 1Department of Ultrasound, Southwest Hospital, Third Military Medical University, Chongqing, People’s Republic of China; 2Department of Urology, Daping Hospital, Institute of Surgery Research, Third Military Medical University, Chongqing, People’s Republic of China Abstract: In this study, the lipid targeted nanobubble carrying the A10-3.2 aptamer against prostate specific membrane antigen was fabricated, and its effect in the ultrasound imaging of prostate cancer was investigated. Materials including 2-dipalmitoyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoyl-sn-glycero-3-phosphatidic acid, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine, 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol, carboxyl-modified 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, and polyethyleneglycol-2000 were for mechanical oscillation, and nanobubbles were obtained through the centrifugal flotation method. After mice were injected with nanobubbles, abdominal color Doppler blood flow imaging significantly improved. Through left ventricular perfusion with normal saline to empty the circulating nanobubbles, nanobubbles still existed in tumor tissue sections, which demonstrated that nanobubbles could enter tissue spaces via the permeability and retention effect. Fluorinated A10-3.2 aptamers obtained by chemical synthesis had good specificity for PSMA-positive cells, and were linked with carboxyl-modified 1,2-distearoyl-sn-glycero-3-phosphoethanolamine lipid molecules from the outer shell of nanobubbles via amide reaction to construct targeted nanobubbles. Gel electrophoresis and immunofluorescence confirmed that targeted nanobubbles were fabricated successfully. Next, targeted nanobubbles could bind with PSMA-positive cells (C4-2 cells), while not with PSMA-negative cells (PC-3 cells), using in vitro binding experiments and flow cytometry at the cellular level. Finally, C4-2 and PC-3 xenografts in mice were used to observe changes in parameters of targeted and non-targeted nanobubbles in the contrast-enhanced ultrasound mode, and the distribution of Cy5.5-labeled targeted nanobubbles in fluorescent imaging of live small animals. Comparison of ultrasound indicators between targeted and non-targeted nanobubbles in C4-2 xenografts showed that they had similar peak times (P>0.05), while the peak intensity, half time of peak intensity, and area under the curve of ½ peak intensity were significantly different (P<0.05). In PC-3 xenografts, there were no differences in these four indicators. Fluorescent imaging indicated that targeted nanobubbles had an aggregation ability in C4-2 xenograft tumors. In conclusion, targeted nanobubbles carrying the anti-PSMA A10-3.2 aptamer have a targeted imaging effect in prostate cancer. Keywords: molecular imaging, contrast-enhanced ultrasound, aptamer, prostate specific membrane antigen, targeted imaging
format	article
author	Fan X Guo Y Wang L Xiong X Zhu L Fang K
author_facet	Fan X Guo Y Wang L Xiong X Zhu L Fang K
author_sort	Fan X
title	Diagnosis of prostate cancer using anti-PSMA aptamer A10-3.2-oriented lipid nanobubbles
title_short	Diagnosis of prostate cancer using anti-PSMA aptamer A10-3.2-oriented lipid nanobubbles
title_full	Diagnosis of prostate cancer using anti-PSMA aptamer A10-3.2-oriented lipid nanobubbles
title_fullStr	Diagnosis of prostate cancer using anti-PSMA aptamer A10-3.2-oriented lipid nanobubbles
title_full_unstemmed	Diagnosis of prostate cancer using anti-PSMA aptamer A10-3.2-oriented lipid nanobubbles
title_sort	diagnosis of prostate cancer using anti-psma aptamer a10-3.2-oriented lipid nanobubbles
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/58c0086336ea4306b32ec63cd2159533
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Diagnosis of prostate cancer using anti-PSMA aptamer A10-3.2-oriented lipid nanobubbles

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