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CAIX aptamer-functionalized targeted nanobubbles for ultrasound molecular imaging of various tumors

PURPOSE: Targeted nanobubbles can penetrate the tumor vasculature and achieve ultrasound molecular imaging (USMI) of tumor parenchymal cells. However, most targeted nanobubbles only achieve USMI of tumor parenchymal cells from one organ, and their distribution, loading ability, and binding ability i...

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Autores principales: Zhu, Lianhua, Wang, Luofu, Liu, Yu, Xu, Dan, Fang, Kejing, Guo, Yanli
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6199208/
https://www.ncbi.nlm.nih.gov/pubmed/30410333
http://dx.doi.org/10.2147/IJN.S176287
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author Zhu, Lianhua
Wang, Luofu
Liu, Yu
Xu, Dan
Fang, Kejing
Guo, Yanli
author_facet Zhu, Lianhua
Wang, Luofu
Liu, Yu
Xu, Dan
Fang, Kejing
Guo, Yanli
author_sort Zhu, Lianhua
collection PubMed
description PURPOSE: Targeted nanobubbles can penetrate the tumor vasculature and achieve ultrasound molecular imaging (USMI) of tumor parenchymal cells. However, most targeted nanobubbles only achieve USMI of tumor parenchymal cells from one organ, and their distribution, loading ability, and binding ability in tumors are not clear. Therefore, targeted nanobubbles loaded with carbonic anhydrase IX (CAIX) aptamer were fabricated for USMI of various tumors, and the morphological basis of USMI with targeted nanobubbles was investigated. MATERIALS AND METHODS: The specificity of CAIX aptamer at the cellular level was measured by immunofluorescence and flow cytometry. Targeted nanobubbles loaded with CAIX aptamer were prepared by a maleimidethiol coupling reaction, and their binding ability to CAIX-positive tumor cells was analyzed in vitro. USMI of targeted and non-targeted nanobubbles was performed in tumor-bearing nude mice. The distribution, loading ability, and binding ability of targeted nanobubbles in xenograft tumor tissues were demonstrated by immunofluorescence. RESULTS: CAIX aptamer could specifically bind to CAIX-positive 786-O and Hela cells, rather than CAIX-negative BxPC-3 cells. Targeted nanobubbles loaded with CAIX aptamer had the advantages of small size, uniform distribution, regular shape, and high safety, and they could specifically accumulate around 786-O and Hela cells, while not binding to BxPC-3 cells in vitro. Targeted nanobubbles had significantly higher peak intensity and larger area under the curve than non-targeted nanobubbles in 786-O and Hela xenograft tumor tissues, while there was no significant difference in the imaging effects of targeted and non-targeted nanobubbles in BxPC-3 xenograft tumor tissues. Immunofluorescence demonstrated targeted nanobubbles could still load CAIX aptamer after penetrating the tumor vasculature and specifically binding to CAIX-positive tumor cells in xenograft tumor tissues. CONCLUSION: Targeted nanobubbles loaded with CAIX aptamer have a good imaging effect in USMI of tumor parenchymal cells, and can improve the accuracy of early diagnosis of malignant tumors from various organs.
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spelling pubmed-61992082018-11-08 CAIX aptamer-functionalized targeted nanobubbles for ultrasound molecular imaging of various tumors Zhu, Lianhua Wang, Luofu Liu, Yu Xu, Dan Fang, Kejing Guo, Yanli Int J Nanomedicine Original Research PURPOSE: Targeted nanobubbles can penetrate the tumor vasculature and achieve ultrasound molecular imaging (USMI) of tumor parenchymal cells. However, most targeted nanobubbles only achieve USMI of tumor parenchymal cells from one organ, and their distribution, loading ability, and binding ability in tumors are not clear. Therefore, targeted nanobubbles loaded with carbonic anhydrase IX (CAIX) aptamer were fabricated for USMI of various tumors, and the morphological basis of USMI with targeted nanobubbles was investigated. MATERIALS AND METHODS: The specificity of CAIX aptamer at the cellular level was measured by immunofluorescence and flow cytometry. Targeted nanobubbles loaded with CAIX aptamer were prepared by a maleimidethiol coupling reaction, and their binding ability to CAIX-positive tumor cells was analyzed in vitro. USMI of targeted and non-targeted nanobubbles was performed in tumor-bearing nude mice. The distribution, loading ability, and binding ability of targeted nanobubbles in xenograft tumor tissues were demonstrated by immunofluorescence. RESULTS: CAIX aptamer could specifically bind to CAIX-positive 786-O and Hela cells, rather than CAIX-negative BxPC-3 cells. Targeted nanobubbles loaded with CAIX aptamer had the advantages of small size, uniform distribution, regular shape, and high safety, and they could specifically accumulate around 786-O and Hela cells, while not binding to BxPC-3 cells in vitro. Targeted nanobubbles had significantly higher peak intensity and larger area under the curve than non-targeted nanobubbles in 786-O and Hela xenograft tumor tissues, while there was no significant difference in the imaging effects of targeted and non-targeted nanobubbles in BxPC-3 xenograft tumor tissues. Immunofluorescence demonstrated targeted nanobubbles could still load CAIX aptamer after penetrating the tumor vasculature and specifically binding to CAIX-positive tumor cells in xenograft tumor tissues. CONCLUSION: Targeted nanobubbles loaded with CAIX aptamer have a good imaging effect in USMI of tumor parenchymal cells, and can improve the accuracy of early diagnosis of malignant tumors from various organs. Dove Medical Press 2018-10-16 /pmc/articles/PMC6199208/ /pubmed/30410333 http://dx.doi.org/10.2147/IJN.S176287 Text en © 2018 Zhu et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Zhu, Lianhua
Wang, Luofu
Liu, Yu
Xu, Dan
Fang, Kejing
Guo, Yanli
CAIX aptamer-functionalized targeted nanobubbles for ultrasound molecular imaging of various tumors
title CAIX aptamer-functionalized targeted nanobubbles for ultrasound molecular imaging of various tumors
title_full CAIX aptamer-functionalized targeted nanobubbles for ultrasound molecular imaging of various tumors
title_fullStr CAIX aptamer-functionalized targeted nanobubbles for ultrasound molecular imaging of various tumors
title_full_unstemmed CAIX aptamer-functionalized targeted nanobubbles for ultrasound molecular imaging of various tumors
title_short CAIX aptamer-functionalized targeted nanobubbles for ultrasound molecular imaging of various tumors
title_sort caix aptamer-functionalized targeted nanobubbles for ultrasound molecular imaging of various tumors
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6199208/
https://www.ncbi.nlm.nih.gov/pubmed/30410333
http://dx.doi.org/10.2147/IJN.S176287
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