Nanobubbles Containing sPD-1 and Ce6 Mediate Combination Immunotherapy and Suppress Hepatocellular Carcinoma in Mice

Yandi Tan,1,* Shiqi Yang,1,* Yao Ma,2 Jinlin Li,1 Qian Xie,1 Chaoqi Liu,1 Yun Zhao1 1Medical College of China Three Gorges University, Yichang, Hubei, People’s Republic of China; 2Department of Ultrasonography, Yichang Central People’s Hospital, Yichang, People’s Republ...

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Autores principales:	Tan Y, Yang S, Ma Y, Li J, Xie Q, Liu C, Zhao Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	immune checkpoint inhibitors ultrasonics drug delivery tumor therapy nanomaterials Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/71ef56ba16654002b65f092fc7cf4d83
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spelling	oai:doaj.org-article:71ef56ba16654002b65f092fc7cf4d832021-12-02T15:00:14ZNanobubbles Containing sPD-1 and Ce6 Mediate Combination Immunotherapy and Suppress Hepatocellular Carcinoma in Mice1178-2013https://doaj.org/article/71ef56ba16654002b65f092fc7cf4d832021-05-01T00:00:00Zhttps://www.dovepress.com/nanobubbles-containing-spd-1-and-ce6-mediate-combination-immunotherapy-peer-reviewed-fulltext-article-IJNhttps://doaj.org/toc/1178-2013Yandi Tan,1,* Shiqi Yang,1,* Yao Ma,2 Jinlin Li,1 Qian Xie,1 Chaoqi Liu,1 Yun Zhao1 1Medical College of China Three Gorges University, Yichang, Hubei, People’s Republic of China; 2Department of Ultrasonography, Yichang Central People’s Hospital, Yichang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yun Zhao; Chaoqi LiuMedical College of China Three Gorges University, Yichang, Hubei, 443000, People’s Republic of ChinaEmail zhaoyun@ctgu.edu.cn; ctgulcq@163.comPurpose: Immune checkpoint inhibitors (ICIs) and sonodynamic therapy (SDT) are types of immunotherapy. In order to combine soluble programmed cell death protein 1 (sPD-1)-mediated immune checkpoint therapy and chlorin e6 (Ce6)-assisted SDT, nanobubbles (NBs) were generated to simultaneously load sPD-1 and Ce6.Materials and Methods: The sPD-1/Ce6-NBs, which were prepared by thin-film hydration and mechanical oscillation, had a stable physical condition, and delivered sPD-1 and Ce6 in a targeted manner. NBs could strengthen tumor suppression by increasing tumor-targeting accumulation of Ce6 and sPD-1, and by inducing ultrasound-targeted NB destruction. A mouse H22 cell hepatoma xenograft model was used to evaluate the synergetic immunotherapeutic effect and mechanism of sPD-1/Ce6-NBs.Results: By observing the tumor inhibition rate, tissue and cell apoptosis, apoptosis-related genes and protein expression, the best immunotherapeutic effect was exhibited by the sPD-1/Ce6-NBs group. The immunotherapeutic mechanism initially demonstrated that when tumor cells were transfected by sPD-1 delivered by NBs, which downregulated the expression of programmed death-ligand 1 (PD-L1) in tumor cells, and blocked the PD-1/PD-L1 signaling pathway, which improved T-cell-mediated tumor inhibition. Furthermore, ICIs combined with SDT induced immunogenic cell death by translocating calreticulin to the cell surface and then synergistically enhancing antitumor immune responses.Conclusion: In conclusion, sPD-1/Ce6-NBs were successfully designed. Ultrasound-mediated sPD-1/Ce6-NBs are potentially effective delivery systems for combination immunotherapy of hepatocellular carcinoma.Keywords: immune checkpoint inhibitors, ultrasonics, drug delivery, tumor therapy, nanomaterialsTan YYang SMa YLi JXie QLiu CZhao YDove Medical Pressarticleimmune checkpoint inhibitorsultrasonicsdrug deliverytumor therapynanomaterialsMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 3241-3254 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	immune checkpoint inhibitors ultrasonics drug delivery tumor therapy nanomaterials Medicine (General) R5-920
spellingShingle	immune checkpoint inhibitors ultrasonics drug delivery tumor therapy nanomaterials Medicine (General) R5-920 Tan Y Yang S Ma Y Li J Xie Q Liu C Zhao Y Nanobubbles Containing sPD-1 and Ce6 Mediate Combination Immunotherapy and Suppress Hepatocellular Carcinoma in Mice
description	Yandi Tan,1,* Shiqi Yang,1,* Yao Ma,2 Jinlin Li,1 Qian Xie,1 Chaoqi Liu,1 Yun Zhao1 1Medical College of China Three Gorges University, Yichang, Hubei, People’s Republic of China; 2Department of Ultrasonography, Yichang Central People’s Hospital, Yichang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yun Zhao; Chaoqi LiuMedical College of China Three Gorges University, Yichang, Hubei, 443000, People’s Republic of ChinaEmail zhaoyun@ctgu.edu.cn; ctgulcq@163.comPurpose: Immune checkpoint inhibitors (ICIs) and sonodynamic therapy (SDT) are types of immunotherapy. In order to combine soluble programmed cell death protein 1 (sPD-1)-mediated immune checkpoint therapy and chlorin e6 (Ce6)-assisted SDT, nanobubbles (NBs) were generated to simultaneously load sPD-1 and Ce6.Materials and Methods: The sPD-1/Ce6-NBs, which were prepared by thin-film hydration and mechanical oscillation, had a stable physical condition, and delivered sPD-1 and Ce6 in a targeted manner. NBs could strengthen tumor suppression by increasing tumor-targeting accumulation of Ce6 and sPD-1, and by inducing ultrasound-targeted NB destruction. A mouse H22 cell hepatoma xenograft model was used to evaluate the synergetic immunotherapeutic effect and mechanism of sPD-1/Ce6-NBs.Results: By observing the tumor inhibition rate, tissue and cell apoptosis, apoptosis-related genes and protein expression, the best immunotherapeutic effect was exhibited by the sPD-1/Ce6-NBs group. The immunotherapeutic mechanism initially demonstrated that when tumor cells were transfected by sPD-1 delivered by NBs, which downregulated the expression of programmed death-ligand 1 (PD-L1) in tumor cells, and blocked the PD-1/PD-L1 signaling pathway, which improved T-cell-mediated tumor inhibition. Furthermore, ICIs combined with SDT induced immunogenic cell death by translocating calreticulin to the cell surface and then synergistically enhancing antitumor immune responses.Conclusion: In conclusion, sPD-1/Ce6-NBs were successfully designed. Ultrasound-mediated sPD-1/Ce6-NBs are potentially effective delivery systems for combination immunotherapy of hepatocellular carcinoma.Keywords: immune checkpoint inhibitors, ultrasonics, drug delivery, tumor therapy, nanomaterials
format	article
author	Tan Y Yang S Ma Y Li J Xie Q Liu C Zhao Y
author_facet	Tan Y Yang S Ma Y Li J Xie Q Liu C Zhao Y
author_sort	Tan Y
title	Nanobubbles Containing sPD-1 and Ce6 Mediate Combination Immunotherapy and Suppress Hepatocellular Carcinoma in Mice
title_short	Nanobubbles Containing sPD-1 and Ce6 Mediate Combination Immunotherapy and Suppress Hepatocellular Carcinoma in Mice
title_full	Nanobubbles Containing sPD-1 and Ce6 Mediate Combination Immunotherapy and Suppress Hepatocellular Carcinoma in Mice
title_fullStr	Nanobubbles Containing sPD-1 and Ce6 Mediate Combination Immunotherapy and Suppress Hepatocellular Carcinoma in Mice
title_full_unstemmed	Nanobubbles Containing sPD-1 and Ce6 Mediate Combination Immunotherapy and Suppress Hepatocellular Carcinoma in Mice
title_sort	nanobubbles containing spd-1 and ce6 mediate combination immunotherapy and suppress hepatocellular carcinoma in mice
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/71ef56ba16654002b65f092fc7cf4d83
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Nanobubbles Containing sPD-1 and Ce6 Mediate Combination Immunotherapy and Suppress Hepatocellular Carcinoma in Mice

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