Multifunctional Nanoparticles Encapsulating Astragalus Polysaccharide and Gold Nanorods in Combination with Focused Ultrasound for the Treatment of Breast Cancer

Jie Xiong,1 Binglei Jiang,1 Yong Luo,1 Jianzhong Zou,1 Xuan Gao,1 Die Xu,1 Yan Du,1,2 Lan Hao3 1State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing Key Laboratory of Biomedical Engineering, Chongqing Medical Unive...

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Autores principales:	Xiong J, Jiang B, Luo Y, Zou J, Gao X, Xu D, Du Y, Hao L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	immune immunoadjuvant thermal ablation plga chinese traditional medicine Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/c67f60ca79014e42b0944318d9096ffd
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spelling	oai:doaj.org-article:c67f60ca79014e42b0944318d9096ffd2021-12-02T10:10:59ZMultifunctional Nanoparticles Encapsulating Astragalus Polysaccharide and Gold Nanorods in Combination with Focused Ultrasound for the Treatment of Breast Cancer1178-2013https://doaj.org/article/c67f60ca79014e42b0944318d9096ffd2020-06-01T00:00:00Zhttps://www.dovepress.com/multifunctional-nanoparticles-encapsulating-astragalus-polysaccharide--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jie Xiong,1 Binglei Jiang,1 Yong Luo,1 Jianzhong Zou,1 Xuan Gao,1 Die Xu,1 Yan Du,1,2 Lan Hao3 1State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing Key Laboratory of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, People’s Republic of China; 2Ultrasonography Department, The Fourth People’s Hospital of Chongqing, Central Hospital of Chongqing University, Chongqing 400014, People’s Republic of China; 3Institute of Ultrasound Imaging, Chongqing Medical University, Chongqing 400010, People’s Republic of ChinaCorrespondence: Jianzhong ZouCollege of Biomedical Engineering, Chongqing Medical University, Chongqing 400010, People’s Republic of ChinaTel +86 13783002390Email zoujzh@cqmu.edu.cnPurpose: Focused ultrasound (FUS) is a noninvasive method to produce thermal and mechanical destruction along with an immune-stimulatory effect against cancer. However, FUS ablation alone appears insufficient to generate consistent antitumor immunity. In this study, a multifunctional nanoparticle was designed to boost FUS-induced immune effects and achieve systemic, long-lasting antitumor immunity, along with imaging and thermal enhancement.Materials and Methods: PEGylated PLGA nanoparticles encapsulating astragalus polysaccharides (APS) and gold nanorods (AuNRs) were constructed by a simple double emulsion method, characterized, and tested for cytotoxicity. The abilities of PA imaging and thermal-synergetic ablation efficiency were analyzed in vitro and in vivo. The immune-synergistic effect on dendritic cell (DC) differentiation in vitro and the immune response in vivo were also evaluated.Results: The obtained APS/AuNR/PLGA-PEG nanoparticles have an average diameter of 255.00± 0.1717 nm and an APS-loading efficiency of 54.89± 2.07%, demonstrating their PA imaging capability and high biocompatibility both in vitro and in vivo. In addition, the as-prepared nanoparticles achieved a higher necrosis cell rate and induced apoptosis rate in an in vitro cell suspension assay, greater necrosis area and decreased energy efficiency factor (EEF) in an in vivo rabbit liver assay, and remarkable thermal-synergic performance. In particular, the nanoparticles upregulated the expression of MHC-II, CD80 and CD86 on cocultured DCs in vitro, followed by declining phagocytic function and enhanced interleukin (IL)-12 and interferon (INF)-γ production. Furthermore, they boosted the production of tumor necrosis factor (TNF)-α, IFN-γ, IL-4, IL-10, and IgG1 (P< 0.001) but not IgG2a. Immune promotion peaked on day 3 after FUS in vivo.Conclusion: The multifunctional APS/AuNR/PLGA-PEG nanoparticles can serve as an excellent synergistic agent for FUS therapy, facilitating real-time imaging, promoting thermal ablation effects, and boosting FUS-induced immune effects, which have the potential to be used for further clinical FUS treatment.Keywords: immune, immunoadjuvant, thermal ablation, PLGA, Chinese traditional medicineXiong JJiang BLuo YZou JGao XXu DDu YHao LDove Medical Pressarticleimmuneimmunoadjuvantthermal ablationplgachinese traditional medicineMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 4151-4169 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	immune immunoadjuvant thermal ablation plga chinese traditional medicine Medicine (General) R5-920
spellingShingle	immune immunoadjuvant thermal ablation plga chinese traditional medicine Medicine (General) R5-920 Xiong J Jiang B Luo Y Zou J Gao X Xu D Du Y Hao L Multifunctional Nanoparticles Encapsulating Astragalus Polysaccharide and Gold Nanorods in Combination with Focused Ultrasound for the Treatment of Breast Cancer
description	Jie Xiong,1 Binglei Jiang,1 Yong Luo,1 Jianzhong Zou,1 Xuan Gao,1 Die Xu,1 Yan Du,1,2 Lan Hao3 1State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing Key Laboratory of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, People’s Republic of China; 2Ultrasonography Department, The Fourth People’s Hospital of Chongqing, Central Hospital of Chongqing University, Chongqing 400014, People’s Republic of China; 3Institute of Ultrasound Imaging, Chongqing Medical University, Chongqing 400010, People’s Republic of ChinaCorrespondence: Jianzhong ZouCollege of Biomedical Engineering, Chongqing Medical University, Chongqing 400010, People’s Republic of ChinaTel +86 13783002390Email zoujzh@cqmu.edu.cnPurpose: Focused ultrasound (FUS) is a noninvasive method to produce thermal and mechanical destruction along with an immune-stimulatory effect against cancer. However, FUS ablation alone appears insufficient to generate consistent antitumor immunity. In this study, a multifunctional nanoparticle was designed to boost FUS-induced immune effects and achieve systemic, long-lasting antitumor immunity, along with imaging and thermal enhancement.Materials and Methods: PEGylated PLGA nanoparticles encapsulating astragalus polysaccharides (APS) and gold nanorods (AuNRs) were constructed by a simple double emulsion method, characterized, and tested for cytotoxicity. The abilities of PA imaging and thermal-synergetic ablation efficiency were analyzed in vitro and in vivo. The immune-synergistic effect on dendritic cell (DC) differentiation in vitro and the immune response in vivo were also evaluated.Results: The obtained APS/AuNR/PLGA-PEG nanoparticles have an average diameter of 255.00± 0.1717 nm and an APS-loading efficiency of 54.89± 2.07%, demonstrating their PA imaging capability and high biocompatibility both in vitro and in vivo. In addition, the as-prepared nanoparticles achieved a higher necrosis cell rate and induced apoptosis rate in an in vitro cell suspension assay, greater necrosis area and decreased energy efficiency factor (EEF) in an in vivo rabbit liver assay, and remarkable thermal-synergic performance. In particular, the nanoparticles upregulated the expression of MHC-II, CD80 and CD86 on cocultured DCs in vitro, followed by declining phagocytic function and enhanced interleukin (IL)-12 and interferon (INF)-γ production. Furthermore, they boosted the production of tumor necrosis factor (TNF)-α, IFN-γ, IL-4, IL-10, and IgG1 (P< 0.001) but not IgG2a. Immune promotion peaked on day 3 after FUS in vivo.Conclusion: The multifunctional APS/AuNR/PLGA-PEG nanoparticles can serve as an excellent synergistic agent for FUS therapy, facilitating real-time imaging, promoting thermal ablation effects, and boosting FUS-induced immune effects, which have the potential to be used for further clinical FUS treatment.Keywords: immune, immunoadjuvant, thermal ablation, PLGA, Chinese traditional medicine
format	article
author	Xiong J Jiang B Luo Y Zou J Gao X Xu D Du Y Hao L
author_facet	Xiong J Jiang B Luo Y Zou J Gao X Xu D Du Y Hao L
author_sort	Xiong J
title	Multifunctional Nanoparticles Encapsulating Astragalus Polysaccharide and Gold Nanorods in Combination with Focused Ultrasound for the Treatment of Breast Cancer
title_short	Multifunctional Nanoparticles Encapsulating Astragalus Polysaccharide and Gold Nanorods in Combination with Focused Ultrasound for the Treatment of Breast Cancer
title_full	Multifunctional Nanoparticles Encapsulating Astragalus Polysaccharide and Gold Nanorods in Combination with Focused Ultrasound for the Treatment of Breast Cancer
title_fullStr	Multifunctional Nanoparticles Encapsulating Astragalus Polysaccharide and Gold Nanorods in Combination with Focused Ultrasound for the Treatment of Breast Cancer
title_full_unstemmed	Multifunctional Nanoparticles Encapsulating Astragalus Polysaccharide and Gold Nanorods in Combination with Focused Ultrasound for the Treatment of Breast Cancer
title_sort	multifunctional nanoparticles encapsulating astragalus polysaccharide and gold nanorods in combination with focused ultrasound for the treatment of breast cancer
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/c67f60ca79014e42b0944318d9096ffd
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Multifunctional Nanoparticles Encapsulating Astragalus Polysaccharide and Gold Nanorods in Combination with Focused Ultrasound for the Treatment of Breast Cancer

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