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

Authors :
Qiu-Chen Bi
Jian-Jun Tang
Jun Zhao
Yang-Feng Lv
Zhi-Qiang Deng
Hong Chen
Yu-Hua Xu
Chuan-Sheng Xie
Qing-Rong Liang
Rong-Guang Luo
Qun Tang
Source :
Drug Delivery; Dec2022, Vol. 29 Issue 1, p1447-1456, 10p
Publication Year :
2022

Abstract

Arsenic trioxide (As<subscript>2</subscript>O<subscript>3</subscript>, 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 (Δwm) 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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
10717544
Volume :
29
Issue :
1
Database :
Complementary Index
Journal :
Drug Delivery
Publication Type :
Academic Journal
Accession number :
161643990
Full Text :
https://doi.org/10.1080/10717544.2022.2072541