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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2022
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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. |
format | Online Article Text |
id | pubmed-9103487 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
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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