&lt;p&gt;Dual-Effect of Magnetic Resonance Imaging Reporter Gene in Diagnosis and Treatment of Hepatocellular Carcinoma&lt;/p&gt;

et al. 2021

J Nanobiotechnol

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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

Section: Resultsmentioning

confidence: 99%

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

et al. 2021

J Nanobiotechnol

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“…5a). This was expected because we have previously demonstrated that the transferrin receptor was overexpressed in HepG2 cells [49]. In addition, the nanoplatform-induced intracellular iron accumulation was also investigated directly with ICP.…”

Section: Evaluation On the Uptake E Ciency Of Nanosamples By Hepg2 Cellsmentioning

confidence: 91%

Self-Amplification of Oxidative Stress with Tumor Microenvironment-Activatable Iron-Doped Nanoplatform for Targeting Hepatocellular Carcinoma Synergistic Cascade Therapy and Diagnosis

et al. 2021

Preprint

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Background The rapid development of hepatocellular carcinoma (HCC) treatment resistance has become a technical bottleneck for clinical treatment. Conventional chemotherapy has long been regarded as ineffective against HCC because of the insensitivity to chemotherapy drugs. Ferroptosis is a form of programmed cell death with a definite Fenton reaction mechanism that converts endogenous hydrogen peroxide (H2O2) into highly toxic hydroxyl radicals (·OH). Therefore, we have developed an ultrasensitive iron-doped magnetic mesoporous silica nanoplatform (DOX@Fe-HMON-Tf NPs) for HCC-targeted synergistic cascade therapy and diagnosis. Results This organic/inorganic nanoplatform consists of a silica shell doped with iron and bis[3-(triethoxysilyl)propyl]tetrasulfide (BTES) and the etched core loaded DOX that generate H2O2 in situ to enhance the ferroptosis effect. DOX@Fe-HMON-Tf NPs can efectively internalized into hepatoma cells by precise delivery through the transferrin grafted with polyethylene glycol (PEG) outside the shell. The resulting nanoplatform can be activated by the tumor microenvironment (TME) in which the glutathione (GSH)-responsive biodegradability could synergize with the therapeutic interaction between DOX and iron and induce tumor cells death through complementary ferroptosis and apoptosis mechanisms. At the same time, the nanoplatform has a superparamagnetic framework that can be used for treatment guidance and monitoring under the guidance of T2-weighted magnetic resonance imaging (MRI). Conclusion The rationally designed nanoplatform provides a new strategy for anti-tumor effects with self-amplified synergistic chemotherapy and chemodynamic therapy (CDT) based on ferroptosis, and magnetic resonance imaging that realizes the integration of diagnosis, treatment and monitoring.

“…5a). This was expected because we have previously demonstrated that the transferrin receptor was overexpressed in HepG2 cells [49]. Furthermore, the ICP was also used directly to study the intracellular iron accumulation induced by the nanosamples.…”

Section: Evaluation Of Uptake E Ciency Of Hepg2 Cells To Nanosamplesmentioning

confidence: 91%

Self-amplification of Oxidative Stress With Tumour Microenvironment-activatable Iron-doped Nanoplatform for Targeting Hepatocellular Carcinoma Synergistic Cascade Therapy and Diagnosis

et al. 2021

Preprint

Background: Hepatocellular carcinoma (HCC) is insensitivity to chemotherapy drugs and conventional chemotherapy has long been regarded as ineffective against HCC. Ferroptosis is a form of programmed cell death with a definite Fenton reaction mechanism that converts endogenous hydrogen peroxide (H2O2) into highly toxic hydroxyl radicals (·OH), expected to inhibit HCC in cooperation with chemotherapy.Methods: The organic/inorganic nanoplatform were characterized by various methods to analyze the morphology, element composition and tumour microenvironment response-ability. Determine the tumour-targeting efficiency and imaging capabilities of nanoplatform through magnetic resonance imaging (MRI) in vivo and in vitro. Confocal microscopy, flow cytometry and western blotting were used to study the therapeutic efficacy and mechanism of complementary ferroptosis/apoptosis treatment of nanoplatform. Results: This nanoplatform consists of a silica shell doped with iron and disulfide bonds, and the etched core loaded DOX that generate H2O2 in situ to enhance the ferroptosis effect. The ultrasensitive nanoplatform relied on transferrin for precise delivery and could be activated by the tumour microenvironment (TME) in which the glutathione (GSH)-responsive biodegradability could synergize with the therapeutic interaction between DOX and iron and induce tumour cells death through complementary ferroptosis and apoptosis mechanisms. Simultaneously, the nanoplatform had a superparamagnetic framework that can be used for treatment guidance and monitoring under the guidance of T2-weighted MRI.Conclusion: The rationally designed nanoplatform is expected to realize the integration of diagnosis, treatment and monitoring, and provides a new strategy for anti-tumour effects.