pH- and Ultrasound-Responsive Paclitaxel-Loaded Carboxymethyl Chitosan Nanodroplets for Combined Imaging and Synergistic Chemoradiotherapy

Mengmeng Shang,1 Xiao Sun,1 Lu Guo,1 Dandan Shi,1 Ping Liang,2 Dong Meng,1 Xiaoying Zhou,1 Xinxin Liu,1 Yading Zhao,1 Jie Li1 1Department of Ultrasound, Qilu Hospital of Shandong University, Jinan 250012, People’s Republic of China; 2Department of Interventional Ultrasound, Chinese PLA Gen...

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Autores principales:	Shang M, Sun X, Guo L, Shi D, Liang P, Meng D, Zhou X, Liu X, Zhao Y, Li J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	nanodroplets ultrasound contrast agents chemoradiotherapy radiosensitizer paclitaxel chitosan Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/9a0689ab3bae4595a503c6fc8f114a29
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spelling	oai:doaj.org-article:9a0689ab3bae4595a503c6fc8f114a292021-12-02T04:16:19ZpH- and Ultrasound-Responsive Paclitaxel-Loaded Carboxymethyl Chitosan Nanodroplets for Combined Imaging and Synergistic Chemoradiotherapy1178-2013https://doaj.org/article/9a0689ab3bae4595a503c6fc8f114a292020-01-01T00:00:00Zhttps://www.dovepress.com/ph--and-ultrasound-responsive-paclitaxel-loaded-carboxymethyl-chitosan-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Mengmeng Shang,1 Xiao Sun,1 Lu Guo,1 Dandan Shi,1 Ping Liang,2 Dong Meng,1 Xiaoying Zhou,1 Xinxin Liu,1 Yading Zhao,1 Jie Li1 1Department of Ultrasound, Qilu Hospital of Shandong University, Jinan 250012, People’s Republic of China; 2Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing 100853, People’s Republic of ChinaCorrespondence: Jie LiDepartment of Ultrasound, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan 250012, People’s Republic of ChinaTel +86-531-82166101Fax +86-531-86927544Email jieli301@163.comBackground: Synergistic chemoradiotherapy (CRT) has become a primary effective curative approach for many solid cancers. However, CRT is still associated with several obstacles, including the increases in side effects and systemic toxicity. Incorporating nanocarriers into CRT is a new and exciting approach to solve these obstacles. The purpose of the present study was to design a unique pH- and ultrasound-responsive perfluoropentane-encapsulated, paclitaxel (PTX)-loaded carboxymethyl chitosan nanodroplets (NDs) for combined imaging and synergistic CRT.Materials and Methods: The NDs were prepared by a homogenization/emulsion method. Their physicochemical properties, echogenicity and biocompatibility were evaluated. PTX-loaded NDs with a high loading efficiency and encapsulation efficiency were prepared and their pH-responsive drug release profile was determined by dialysis sack method. Then, PC3 cells were exposed to (1) PTX (4 μg/mL), (2) NDs (30 μg/mL), (3) PTX-loaded NDs (34 μg/mL), (4) RT (6 Gy), (5) RT (10 Gy), (6) combination of PTX (4 μg/mL), ultrasound (0.5 W/cm2, 30 s) and RT (6 Gy), (7) combination of NDs (30 μg/mL), ultrasound (0.5 W/cm2, 30 s) and RT (6Gy), (8) combination of PTX-loaded NDs (30 μg/mL), ultrasound (0.5 W/cm2, 30 s) and RT (6 Gy). 24 hrs later, CCK-8 assay, flow cytometry and migration assay were carried out to evaluate their therapeutic effects in CRT.Results: The desired NDs were successfully prepared, which were with round, spherical shapes, relatively smooth surfaces, core-shell structures and uniform in sizes (< 300 nm with PDI< 0.3 when at pH≧6.0). The NDs exhibited good abilities in pH-dependent charge conversion, biocompatibility and ultrasound contrast echogenicity. The in vitro drug release from PTX-loaded NDs (the highest loading efficiency and encapsulation efficiency were 20.35% and 91.58%) was pH dependent and exhibited an initial burst followed by a sustained drug release. The results of the CCK-8 assay, flow cytometry and migration assay all showed PTX-loaded NDs combined ultrasound and RT significantly enhanced cell responses in CRT.Conclusion: The pH- and ultrasound-responsive PTX-loaded NDs, which exhibited a high echogenicity, drug delivery ability and radiosensitization ability, could be a feasible option for combined imaging and novel enhancing approach in synergistic CRT.Keywords: nanodroplets, ultrasound contrast agents, chemoradiotherapy, radiosensitizer, paclitaxel, chitosanShang MSun XGuo LShi DLiang PMeng DZhou XLiu XZhao YLi JDove Medical Pressarticlenanodropletsultrasound contrast agentschemoradiotherapyradiosensitizerpaclitaxelchitosanMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 537-552 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	nanodroplets ultrasound contrast agents chemoradiotherapy radiosensitizer paclitaxel chitosan Medicine (General) R5-920
spellingShingle	nanodroplets ultrasound contrast agents chemoradiotherapy radiosensitizer paclitaxel chitosan Medicine (General) R5-920 Shang M Sun X Guo L Shi D Liang P Meng D Zhou X Liu X Zhao Y Li J pH- and Ultrasound-Responsive Paclitaxel-Loaded Carboxymethyl Chitosan Nanodroplets for Combined Imaging and Synergistic Chemoradiotherapy
description	Mengmeng Shang,1 Xiao Sun,1 Lu Guo,1 Dandan Shi,1 Ping Liang,2 Dong Meng,1 Xiaoying Zhou,1 Xinxin Liu,1 Yading Zhao,1 Jie Li1 1Department of Ultrasound, Qilu Hospital of Shandong University, Jinan 250012, People’s Republic of China; 2Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing 100853, People’s Republic of ChinaCorrespondence: Jie LiDepartment of Ultrasound, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan 250012, People’s Republic of ChinaTel +86-531-82166101Fax +86-531-86927544Email jieli301@163.comBackground: Synergistic chemoradiotherapy (CRT) has become a primary effective curative approach for many solid cancers. However, CRT is still associated with several obstacles, including the increases in side effects and systemic toxicity. Incorporating nanocarriers into CRT is a new and exciting approach to solve these obstacles. The purpose of the present study was to design a unique pH- and ultrasound-responsive perfluoropentane-encapsulated, paclitaxel (PTX)-loaded carboxymethyl chitosan nanodroplets (NDs) for combined imaging and synergistic CRT.Materials and Methods: The NDs were prepared by a homogenization/emulsion method. Their physicochemical properties, echogenicity and biocompatibility were evaluated. PTX-loaded NDs with a high loading efficiency and encapsulation efficiency were prepared and their pH-responsive drug release profile was determined by dialysis sack method. Then, PC3 cells were exposed to (1) PTX (4 μg/mL), (2) NDs (30 μg/mL), (3) PTX-loaded NDs (34 μg/mL), (4) RT (6 Gy), (5) RT (10 Gy), (6) combination of PTX (4 μg/mL), ultrasound (0.5 W/cm2, 30 s) and RT (6 Gy), (7) combination of NDs (30 μg/mL), ultrasound (0.5 W/cm2, 30 s) and RT (6Gy), (8) combination of PTX-loaded NDs (30 μg/mL), ultrasound (0.5 W/cm2, 30 s) and RT (6 Gy). 24 hrs later, CCK-8 assay, flow cytometry and migration assay were carried out to evaluate their therapeutic effects in CRT.Results: The desired NDs were successfully prepared, which were with round, spherical shapes, relatively smooth surfaces, core-shell structures and uniform in sizes (< 300 nm with PDI< 0.3 when at pH≧6.0). The NDs exhibited good abilities in pH-dependent charge conversion, biocompatibility and ultrasound contrast echogenicity. The in vitro drug release from PTX-loaded NDs (the highest loading efficiency and encapsulation efficiency were 20.35% and 91.58%) was pH dependent and exhibited an initial burst followed by a sustained drug release. The results of the CCK-8 assay, flow cytometry and migration assay all showed PTX-loaded NDs combined ultrasound and RT significantly enhanced cell responses in CRT.Conclusion: The pH- and ultrasound-responsive PTX-loaded NDs, which exhibited a high echogenicity, drug delivery ability and radiosensitization ability, could be a feasible option for combined imaging and novel enhancing approach in synergistic CRT.Keywords: nanodroplets, ultrasound contrast agents, chemoradiotherapy, radiosensitizer, paclitaxel, chitosan
format	article
author	Shang M Sun X Guo L Shi D Liang P Meng D Zhou X Liu X Zhao Y Li J
author_facet	Shang M Sun X Guo L Shi D Liang P Meng D Zhou X Liu X Zhao Y Li J
author_sort	Shang M
title	pH- and Ultrasound-Responsive Paclitaxel-Loaded Carboxymethyl Chitosan Nanodroplets for Combined Imaging and Synergistic Chemoradiotherapy
title_short	pH- and Ultrasound-Responsive Paclitaxel-Loaded Carboxymethyl Chitosan Nanodroplets for Combined Imaging and Synergistic Chemoradiotherapy
title_full	pH- and Ultrasound-Responsive Paclitaxel-Loaded Carboxymethyl Chitosan Nanodroplets for Combined Imaging and Synergistic Chemoradiotherapy
title_fullStr	pH- and Ultrasound-Responsive Paclitaxel-Loaded Carboxymethyl Chitosan Nanodroplets for Combined Imaging and Synergistic Chemoradiotherapy
title_full_unstemmed	pH- and Ultrasound-Responsive Paclitaxel-Loaded Carboxymethyl Chitosan Nanodroplets for Combined Imaging and Synergistic Chemoradiotherapy
title_sort	ph- and ultrasound-responsive paclitaxel-loaded carboxymethyl chitosan nanodroplets for combined imaging and synergistic chemoradiotherapy
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/9a0689ab3bae4595a503c6fc8f114a29
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pH- and Ultrasound-Responsive Paclitaxel-Loaded Carboxymethyl Chitosan Nanodroplets for Combined Imaging and Synergistic Chemoradiotherapy

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