Biodegradable Nanosonosensitizers with the Multiple Modulation of Tumor Microenvironment for Enhanced Sonodynamic Therapy

Hang Zhou,1,2,* Jiawei Sun,1,* Jiaqi Wu,1 Hong Wei,1 Xianli Zhou1 1In-Patient Ultrasound Department, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150081, People’s Republic of China; 2Department of Ultrasound, Second Affiliated Hospital of Zhejiang Universi...

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Autores principales:	Zhou H, Sun J, Wu J, Wei H, Zhou X
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	sonodynamic therapy hypoxia tumor associated macrophages catalase glutathione depletion Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/ea3b5348f1ad4eeba99914a5901c484e
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spelling	oai:doaj.org-article:ea3b5348f1ad4eeba99914a5901c484e2021-12-02T16:57:56ZBiodegradable Nanosonosensitizers with the Multiple Modulation of Tumor Microenvironment for Enhanced Sonodynamic Therapy1178-2013https://doaj.org/article/ea3b5348f1ad4eeba99914a5901c484e2021-04-01T00:00:00Zhttps://www.dovepress.com/biodegradable-nanosonosensitizers-with-the-multiple-modulation-of-tumo-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Hang Zhou,1,2,* Jiawei Sun,1,* Jiaqi Wu,1 Hong Wei,1 Xianli Zhou1 1In-Patient Ultrasound Department, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150081, People’s Republic of China; 2Department of Ultrasound, Second Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang, 310058, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xianli ZhouIn-Patient Ultrasound Department, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150081, People’s Republic of ChinaTel/Fax +86-0451-86605362Email hrbzhouxl@163.comBackground: The specific microenvironment of solid tumors, which is characterized by hypoxia, overexpression of glutathione (GSH), and high accumulation of anti-inflammatory tumor-associated macrophages (TAMs), limits the efficiency of sonodynamic therapy (SDT).Method and Results: Herein, a multifunctional nanoplatform was engineered to modulate the tumor microenvironment for highly efficient SDT. In this system, sonosensitizers and catalase were encapsulated in disulfide-bridged mesoporous organosilicon nanoparticles with high loading, which protected the activity of catalase and ensure the stability of sonosensitizers and enzyme. Subsequently, hyaluronic acid was grafted onto the nanoplatform to reeducate TAMs and induce the secretion of exogenous hydrogen peroxide. Due to the good protection of enzyme, the catalase within the nanoplatform efficiently produced the mount of O2 through decomposing the hydrogen peroxide in tumor tissues, which remarkably alleviated tumor hypoxia. Furthermore, degradation of the nanoparticles was observed in response to GSH, which effectively decreased the intracellular GSH level, further favoring SDT-triggered anticancer effect.Conclusion: Based on the multiple adjustments to tumor microenvironment, our nanoplatform displayed extraordinary sonodynamic therapeutic effect with low systemic toxicity.Keywords: sonodynamic therapy, hypoxia, tumor-associated macrophages, catalase, glutathione depletionZhou HSun JWu JWei HZhou XDove Medical Pressarticlesonodynamic therapyhypoxiatumor associated macrophagescatalaseglutathione depletionMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 2633-2646 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	sonodynamic therapy hypoxia tumor associated macrophages catalase glutathione depletion Medicine (General) R5-920
spellingShingle	sonodynamic therapy hypoxia tumor associated macrophages catalase glutathione depletion Medicine (General) R5-920 Zhou H Sun J Wu J Wei H Zhou X Biodegradable Nanosonosensitizers with the Multiple Modulation of Tumor Microenvironment for Enhanced Sonodynamic Therapy
description	Hang Zhou,1,2,* Jiawei Sun,1,* Jiaqi Wu,1 Hong Wei,1 Xianli Zhou1 1In-Patient Ultrasound Department, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150081, People’s Republic of China; 2Department of Ultrasound, Second Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang, 310058, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xianli ZhouIn-Patient Ultrasound Department, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150081, People’s Republic of ChinaTel/Fax +86-0451-86605362Email hrbzhouxl@163.comBackground: The specific microenvironment of solid tumors, which is characterized by hypoxia, overexpression of glutathione (GSH), and high accumulation of anti-inflammatory tumor-associated macrophages (TAMs), limits the efficiency of sonodynamic therapy (SDT).Method and Results: Herein, a multifunctional nanoplatform was engineered to modulate the tumor microenvironment for highly efficient SDT. In this system, sonosensitizers and catalase were encapsulated in disulfide-bridged mesoporous organosilicon nanoparticles with high loading, which protected the activity of catalase and ensure the stability of sonosensitizers and enzyme. Subsequently, hyaluronic acid was grafted onto the nanoplatform to reeducate TAMs and induce the secretion of exogenous hydrogen peroxide. Due to the good protection of enzyme, the catalase within the nanoplatform efficiently produced the mount of O2 through decomposing the hydrogen peroxide in tumor tissues, which remarkably alleviated tumor hypoxia. Furthermore, degradation of the nanoparticles was observed in response to GSH, which effectively decreased the intracellular GSH level, further favoring SDT-triggered anticancer effect.Conclusion: Based on the multiple adjustments to tumor microenvironment, our nanoplatform displayed extraordinary sonodynamic therapeutic effect with low systemic toxicity.Keywords: sonodynamic therapy, hypoxia, tumor-associated macrophages, catalase, glutathione depletion
format	article
author	Zhou H Sun J Wu J Wei H Zhou X
author_facet	Zhou H Sun J Wu J Wei H Zhou X
author_sort	Zhou H
title	Biodegradable Nanosonosensitizers with the Multiple Modulation of Tumor Microenvironment for Enhanced Sonodynamic Therapy
title_short	Biodegradable Nanosonosensitizers with the Multiple Modulation of Tumor Microenvironment for Enhanced Sonodynamic Therapy
title_full	Biodegradable Nanosonosensitizers with the Multiple Modulation of Tumor Microenvironment for Enhanced Sonodynamic Therapy
title_fullStr	Biodegradable Nanosonosensitizers with the Multiple Modulation of Tumor Microenvironment for Enhanced Sonodynamic Therapy
title_full_unstemmed	Biodegradable Nanosonosensitizers with the Multiple Modulation of Tumor Microenvironment for Enhanced Sonodynamic Therapy
title_sort	biodegradable nanosonosensitizers with the multiple modulation of tumor microenvironment for enhanced sonodynamic therapy
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/ea3b5348f1ad4eeba99914a5901c484e
work_keys_str_mv	AT zhouh biodegradablenanosonosensitizerswiththemultiplemodulationoftumormicroenvironmentforenhancedsonodynamictherapy AT sunj biodegradablenanosonosensitizerswiththemultiplemodulationoftumormicroenvironmentforenhancedsonodynamictherapy AT wuj biodegradablenanosonosensitizerswiththemultiplemodulationoftumormicroenvironmentforenhancedsonodynamictherapy AT weih biodegradablenanosonosensitizerswiththemultiplemodulationoftumormicroenvironmentforenhancedsonodynamictherapy AT zhoux biodegradablenanosonosensitizerswiththemultiplemodulationoftumormicroenvironmentforenhancedsonodynamictherapy
_version_	1718382480194535424

Biodegradable Nanosonosensitizers with the Multiple Modulation of Tumor Microenvironment for Enhanced Sonodynamic Therapy

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