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Sevelamer arsenite nanoparticle as a Pi-responsive drug carrier and embolic agent for chemoembolization

Arsenic trioxide (As(2)O(3), ATO) has limited therapeutic benefit to treat solid tumors, whether used alone or in combination. Nanoscale drug delivery vehicles have great potential to overcome the limitation of the utility of ATO by rapid renal clearance and dose-limiting toxicity. Polymeric materia...

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Autores principales: Bi, Qiu-Chen, Tang, Jian-Jun, Zhao, Jun, Lv, Yang-Feng, Deng, Zhi-Qiang, Chen, Hong, Xu, Yu-Hua, Xie, Chuan-Sheng, Liang, Qing-Rong, Luo, Rong-Guang, Tang, Qun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9103487/
https://www.ncbi.nlm.nih.gov/pubmed/35532152
http://dx.doi.org/10.1080/10717544.2022.2072541
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author Bi, Qiu-Chen
Tang, Jian-Jun
Zhao, Jun
Lv, Yang-Feng
Deng, Zhi-Qiang
Chen, Hong
Xu, Yu-Hua
Xie, Chuan-Sheng
Liang, Qing-Rong
Luo, Rong-Guang
Tang, Qun
author_facet Bi, Qiu-Chen
Tang, Jian-Jun
Zhao, Jun
Lv, Yang-Feng
Deng, Zhi-Qiang
Chen, Hong
Xu, Yu-Hua
Xie, Chuan-Sheng
Liang, Qing-Rong
Luo, Rong-Guang
Tang, Qun
author_sort Bi, Qiu-Chen
collection PubMed
description Arsenic trioxide (As(2)O(3), ATO) has limited therapeutic benefit to treat solid tumors, whether used alone or in combination. Nanoscale drug delivery vehicles have great potential to overcome the limitation of the utility of ATO by rapid renal clearance and dose-limiting toxicity. Polymeric materials ranging from gelatin foam to synthetic polymers such as poly(vinyl alcohol) were developed for vascular embolic or chemoembolic applications. Recently, we have introduced sevelamer, an oral phosphate binder, as a new polymeric embolic for vascular interventional therapy. In this paper, sevelamer arsenite nanoparticle with a polygonal shape and a size of 50–300 nm, synthesized by anionic exchange from sevelamer chloride, was developed as a Pi-responsive bifunctional drug carrier and embolic agent for chemoembolization therapy. At the same arsenic dosage, sevelamer arsenite-induced severer tumor necrosis than ATO on the VX2 cancer model. In vitro tests evidenced that Pi deprivation by sevelamer could enhance ATO’s anticancer effect. The results showed that ATO in Pi starvation reduced cell viability, induced more apoptosis, and diminished the mitochondrial membrane potential (Δψm) of cells since Pi starvation helps ATO to further down-regulate Bcl-2 expression, up-regulate Bax expression, enhance the activation of caspase-3 and increase the release of cytochrome c, and the production of excessive reactive oxygen species (ROS). Sevelamer arsenite not only plays a Pi-activated nano-drug delivery system but also integrated anticancer drug with embolic for interventional therapy. Therefore, our results presented a new administration route of ATO as well as an alternative chemoembolization therapy.
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spelling pubmed-91034872022-05-14 Sevelamer arsenite nanoparticle as a Pi-responsive drug carrier and embolic agent for chemoembolization Bi, Qiu-Chen Tang, Jian-Jun Zhao, Jun Lv, Yang-Feng Deng, Zhi-Qiang Chen, Hong Xu, Yu-Hua Xie, Chuan-Sheng Liang, Qing-Rong Luo, Rong-Guang Tang, Qun Drug Deliv Research Article Arsenic trioxide (As(2)O(3), ATO) has limited therapeutic benefit to treat solid tumors, whether used alone or in combination. Nanoscale drug delivery vehicles have great potential to overcome the limitation of the utility of ATO by rapid renal clearance and dose-limiting toxicity. Polymeric materials ranging from gelatin foam to synthetic polymers such as poly(vinyl alcohol) were developed for vascular embolic or chemoembolic applications. Recently, we have introduced sevelamer, an oral phosphate binder, as a new polymeric embolic for vascular interventional therapy. In this paper, sevelamer arsenite nanoparticle with a polygonal shape and a size of 50–300 nm, synthesized by anionic exchange from sevelamer chloride, was developed as a Pi-responsive bifunctional drug carrier and embolic agent for chemoembolization therapy. At the same arsenic dosage, sevelamer arsenite-induced severer tumor necrosis than ATO on the VX2 cancer model. In vitro tests evidenced that Pi deprivation by sevelamer could enhance ATO’s anticancer effect. The results showed that ATO in Pi starvation reduced cell viability, induced more apoptosis, and diminished the mitochondrial membrane potential (Δψm) of cells since Pi starvation helps ATO to further down-regulate Bcl-2 expression, up-regulate Bax expression, enhance the activation of caspase-3 and increase the release of cytochrome c, and the production of excessive reactive oxygen species (ROS). Sevelamer arsenite not only plays a Pi-activated nano-drug delivery system but also integrated anticancer drug with embolic for interventional therapy. Therefore, our results presented a new administration route of ATO as well as an alternative chemoembolization therapy. Taylor & Francis 2022-05-09 /pmc/articles/PMC9103487/ /pubmed/35532152 http://dx.doi.org/10.1080/10717544.2022.2072541 Text en © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Bi, Qiu-Chen
Tang, Jian-Jun
Zhao, Jun
Lv, Yang-Feng
Deng, Zhi-Qiang
Chen, Hong
Xu, Yu-Hua
Xie, Chuan-Sheng
Liang, Qing-Rong
Luo, Rong-Guang
Tang, Qun
Sevelamer arsenite nanoparticle as a Pi-responsive drug carrier and embolic agent for chemoembolization
title Sevelamer arsenite nanoparticle as a Pi-responsive drug carrier and embolic agent for chemoembolization
title_full Sevelamer arsenite nanoparticle as a Pi-responsive drug carrier and embolic agent for chemoembolization
title_fullStr Sevelamer arsenite nanoparticle as a Pi-responsive drug carrier and embolic agent for chemoembolization
title_full_unstemmed Sevelamer arsenite nanoparticle as a Pi-responsive drug carrier and embolic agent for chemoembolization
title_short Sevelamer arsenite nanoparticle as a Pi-responsive drug carrier and embolic agent for chemoembolization
title_sort sevelamer arsenite nanoparticle as a pi-responsive drug carrier and embolic agent for chemoembolization
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9103487/
https://www.ncbi.nlm.nih.gov/pubmed/35532152
http://dx.doi.org/10.1080/10717544.2022.2072541
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