Self-amplification of oxidative stress with tumour microenvironment-activatable iron-doped nanoplatform for targeting hepatocellular carcinoma synergistic cascade therapy and diagnosis

Abstract Background Hepatocellular carcinoma is insensitive to many chemotherapeutic agents. Ferroptosis is a form of programmed cell death with a Fenton reaction mechanism. It converts endogenous hydrogen peroxide into highly toxic hydroxyl radicals, which inhibit hepatocellular carcinoma progressi...

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Autores principales:	Qiao-Mei Zhou, Yuan-Fei Lu, Jia-Ping Zhou, Xiao-Yan Yang, Xiao-Jie Wang, Jie-Ni Yu, Yong-Zhong Du, Ri-Sheng Yu
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Chemodynamic therapy Ferroptosis Hepatocellular carcinoma Magnetic resonance imaging Organic/inorganic nanoplatform Biotechnology TP248.13-248.65 Medical technology R855-855.5
Acceso en línea:	https://doaj.org/article/e4d630bf084040b895b06c2b4b80c206
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spelling	oai:doaj.org-article:e4d630bf084040b895b06c2b4b80c2062021-11-14T12:29:28ZSelf-amplification of oxidative stress with tumour microenvironment-activatable iron-doped nanoplatform for targeting hepatocellular carcinoma synergistic cascade therapy and diagnosis10.1186/s12951-021-01102-01477-3155https://doaj.org/article/e4d630bf084040b895b06c2b4b80c2062021-11-01T00:00:00Zhttps://doi.org/10.1186/s12951-021-01102-0https://doaj.org/toc/1477-3155Abstract Background Hepatocellular carcinoma is insensitive to many chemotherapeutic agents. Ferroptosis is a form of programmed cell death with a Fenton reaction mechanism. It converts endogenous hydrogen peroxide into highly toxic hydroxyl radicals, which inhibit hepatocellular carcinoma progression. Methods The morphology, elemental composition, and tumour microenvironment responses of various organic/inorganic nanoplatforms were characterised by different analytical methods. Their in vivo and in vitro tumour-targeting efficacy and imaging capability were analysed by magnetic resonance imaging. Confocal microscopy, flow cytometry, and western blotting were used to investigate the therapeutic efficacy and mechanisms of complementary ferroptosis/apoptosis mediated by the nanoplatforms. Results The nanoplatform consisted of a silica shell doped with iron and disulphide bonds and an etched core loaded with doxorubicin that generates hydrogen peroxide in situ and enhances ferroptosis. It relied upon transferrin for targeted drug delivery and could be activated by the tumour microenvironment. Glutathione-responsive biodegradability could operate synergistically with the therapeutic interaction between doxorubicin and iron and induce tumour cell death through complementary ferroptosis and apoptosis. The nanoplatform also has a superparamagnetic framework that could serve to guide and monitor treatment under T2-weighted magnetic resonance imaging. Conclusion This rationally designed nanoplatform is expected to integrate cancer diagnosis, treatment, and monitoring and provide a novel clinical antitumour therapeutic strategy. Graphical AbstractQiao-Mei ZhouYuan-Fei LuJia-Ping ZhouXiao-Yan YangXiao-Jie WangJie-Ni YuYong-Zhong DuRi-Sheng YuBMCarticleChemodynamic therapyFerroptosisHepatocellular carcinomaMagnetic resonance imagingOrganic/inorganic nanoplatformBiotechnologyTP248.13-248.65Medical technologyR855-855.5ENJournal of Nanobiotechnology, Vol 19, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Chemodynamic therapy Ferroptosis Hepatocellular carcinoma Magnetic resonance imaging Organic/inorganic nanoplatform Biotechnology TP248.13-248.65 Medical technology R855-855.5
spellingShingle	Chemodynamic therapy Ferroptosis Hepatocellular carcinoma Magnetic resonance imaging Organic/inorganic nanoplatform Biotechnology TP248.13-248.65 Medical technology R855-855.5 Qiao-Mei Zhou Yuan-Fei Lu Jia-Ping Zhou Xiao-Yan Yang Xiao-Jie Wang Jie-Ni Yu Yong-Zhong Du Ri-Sheng Yu Self-amplification of oxidative stress with tumour microenvironment-activatable iron-doped nanoplatform for targeting hepatocellular carcinoma synergistic cascade therapy and diagnosis
description	Abstract Background Hepatocellular carcinoma is insensitive to many chemotherapeutic agents. Ferroptosis is a form of programmed cell death with a Fenton reaction mechanism. It converts endogenous hydrogen peroxide into highly toxic hydroxyl radicals, which inhibit hepatocellular carcinoma progression. Methods The morphology, elemental composition, and tumour microenvironment responses of various organic/inorganic nanoplatforms were characterised by different analytical methods. Their in vivo and in vitro tumour-targeting efficacy and imaging capability were analysed by magnetic resonance imaging. Confocal microscopy, flow cytometry, and western blotting were used to investigate the therapeutic efficacy and mechanisms of complementary ferroptosis/apoptosis mediated by the nanoplatforms. Results The nanoplatform consisted of a silica shell doped with iron and disulphide bonds and an etched core loaded with doxorubicin that generates hydrogen peroxide in situ and enhances ferroptosis. It relied upon transferrin for targeted drug delivery and could be activated by the tumour microenvironment. Glutathione-responsive biodegradability could operate synergistically with the therapeutic interaction between doxorubicin and iron and induce tumour cell death through complementary ferroptosis and apoptosis. The nanoplatform also has a superparamagnetic framework that could serve to guide and monitor treatment under T2-weighted magnetic resonance imaging. Conclusion This rationally designed nanoplatform is expected to integrate cancer diagnosis, treatment, and monitoring and provide a novel clinical antitumour therapeutic strategy. Graphical Abstract
format	article
author	Qiao-Mei Zhou Yuan-Fei Lu Jia-Ping Zhou Xiao-Yan Yang Xiao-Jie Wang Jie-Ni Yu Yong-Zhong Du Ri-Sheng Yu
author_facet	Qiao-Mei Zhou Yuan-Fei Lu Jia-Ping Zhou Xiao-Yan Yang Xiao-Jie Wang Jie-Ni Yu Yong-Zhong Du Ri-Sheng Yu
author_sort	Qiao-Mei Zhou
title	Self-amplification of oxidative stress with tumour microenvironment-activatable iron-doped nanoplatform for targeting hepatocellular carcinoma synergistic cascade therapy and diagnosis
title_short	Self-amplification of oxidative stress with tumour microenvironment-activatable iron-doped nanoplatform for targeting hepatocellular carcinoma synergistic cascade therapy and diagnosis
title_full	Self-amplification of oxidative stress with tumour microenvironment-activatable iron-doped nanoplatform for targeting hepatocellular carcinoma synergistic cascade therapy and diagnosis
title_fullStr	Self-amplification of oxidative stress with tumour microenvironment-activatable iron-doped nanoplatform for targeting hepatocellular carcinoma synergistic cascade therapy and diagnosis
title_full_unstemmed	Self-amplification of oxidative stress with tumour microenvironment-activatable iron-doped nanoplatform for targeting hepatocellular carcinoma synergistic cascade therapy and diagnosis
title_sort	self-amplification of oxidative stress with tumour microenvironment-activatable iron-doped nanoplatform for targeting hepatocellular carcinoma synergistic cascade therapy and diagnosis
publisher	BMC
publishDate	2021
url	https://doaj.org/article/e4d630bf084040b895b06c2b4b80c206
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Self-amplification of oxidative stress with tumour microenvironment-activatable iron-doped nanoplatform for targeting hepatocellular carcinoma synergistic cascade therapy and diagnosis

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