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

Journal of Nanobiotechnology

Jia-Ping Zhou¹  Xiao-Yan Yang¹  Yuan-Fei Lu¹  Qiao-Mei Zhou¹  Xiao-Jie Wang¹  Jie-Ni Yu¹  Ri-Sheng Yu¹  Yong-Zhong Du² 

[1] Department of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, 310009, Hangzhou, Zhejiang Province, People’s Republic of China;Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, 310058, Hangzhou, Zhejiang Province, People’s Republic of China;

关键词: Chemodynamic therapy;    Ferroptosis;    Hepatocellular carcinoma;    Magnetic resonance imaging;    Organic/inorganic nanoplatform;   

DOI  :  10.1186/s12951-021-01102-0

来源: Springer

【 摘 要 】

BackgroundHepatocellular 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.MethodsThe 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.ResultsThe 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.ConclusionThis rationally designed nanoplatform is expected to integrate cancer diagnosis, treatment, and monitoring and provide a novel clinical antitumour therapeutic strategy.Graphical Abstract

【 授权许可】

CC BY