Nanocatalytic Theranostics with Glutathione Depletion and Enhanced Reactive Oxygen Species Generation for Efficient Cancer Therapy

Fu, Lian‐Hua; Wan, Yilin; Qi, Chao; He, Jin; Li, Chunying; Yang, Chen; Xu, Han; Lin, Jing; Huang, Peng

doi:10.1002/adma.202006892

Cited by 588 publications

(400 citation statements)

References 47 publications

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“…It was widely accepted that iron ions catalyzed H 2 O 2 to produce •OH via the Fenton reaction. [32][33][34][35][36] We chose 3,3',5,5'-tetramethylbenzidine (TMB) as •OH probe, which could be oxidized to oxTMB with an absorbance at nm. 32 The following control experiment was implemented to eliminate the possibility that MnS catalyzed the conversion of H 2 O 2 to 1 O 2 and affected the chromogenic reaction of TMB (Figure S10).…”

Section: Mri Ros Evaluation Gsh Depletion and Degradation Of Mnsmh Npsmentioning

confidence: 99%

Dual Reactive Oxygen Species Generator Independent of Light and Oxygen for Tumor Imaging and Catalytic Therapy

et al. 2022

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Currently, reactive oxygen species (ROS) generation primarily depends upon light and O 2 , which hampers its further biomedical application. Here, we reported that a manganese(III) salen-based complex (MnS) could continuously catalyze overexpressed hydrogen peroxide (H 2 O 2 ) in the tumor microenvironment to 1 O 2 , while the nanocarrier (MIL-100) as a Fenton reagent could convert H 2 O 2 to hydroxyl radicals (•OH) through the Fenton reaction, inducing noticeable intracellular DNA strand scission and lipid peroxidation to provoke tumor cell apoptosis without the involvement of light and O 2 .Moreover, MIL-100 depleted the antioxidant glutathione, further amplifying intracellular oxidative pressure, which in turn led to the self-degradation of MIL-100, suggesting the long-term biosafety of the nanoplatform. Owing to the excellent magnetic resonance imaging performance of MnS, the diagnosis and specific treatment of tumors were eventually achieved. This work provided a novel approach for the realization of effective tumor catalytic therapy independent of light and O 2 and a promising reference for the development of a wide range of catalytic therapeutic agents.

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Section: Mri Ros Evaluation Gsh Depletion and Degradation Of Mnsmh Npsmentioning

confidence: 99%

Dual Reactive Oxygen Species Generator Independent of Light and Oxygen for Tumor Imaging and Catalytic Therapy

et al. 2022

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“…The resulting Cu-MOF/GOD@HA nanocomposites are activated by GSH in tumors and catalyze H 2 O 2 to produce •OH for CDT for cancer treatment as illustrated in Figure 1. the Cu(II) to Cu(I), which is beneficial for CDT [14]. Therefore, Cu-based nanotherapeutic agents for CDT have attracted a lot of attention.…”

Section: Introductionmentioning

confidence: 99%

Construction of Novel Nanocomposites (Cu-MOF/GOD@HA) for Chemodynamic Therapy

Hao

Shu

et al. 2021

Nanomaterials

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The emerging chemodynamic therapy (CDT) has received an extensive attention in recent years. However, the efficiency of CDT is influenced due to the limitation of H2O2 in tumor. In this study, we designed and synthesized a novel core-shell nanostructure, Cu-metal organic framework (Cu-MOF)/glucose oxidase (GOD)@hyaluronic acid (HA) (Cu-MOF/GOD@HA) for the purpose of improving CDT efficacy by increasing H2O2 concentration and cancer cell targeting. In this design, Cu-MOF act as a CDT agent and GOD carrier. Cu(II) in Cu-MOF are reduced to Cu(I) by GSH to obtain Cu(I)-MOF while GSH is depleted. The depletion of GSH reinforces the concentration of H2O2 in tumor to improve the efficiency of CDT. The resultant Cu(I)-MOF catalyze H2O2 to generate hydroxyl radicals (·OH) for CDT. GOD can catalyze glucose (Glu) to supply H2O2 for CDT enhancement. HA act as a targeting molecule to improve the targeting ability of Cu-MOF/GOD@HA to the tumor cells. In addition, after loading with GOD and coating with HA, the proportion of Cu(I) in Cu-MOF/GOD@HA is increased compared with the proportion of Cu(I) in Cu-MOF. This phenomenon may shorten the reactive time from Cu-MOF to Cu(I)-MOF. The CDT enhancement as a result of GOD and HA effects in Cu-MOF/GOD@HA was evidenced by in vitro cell and in vivo animal studies.

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“…In addition, high concentration of glutathione (GSH) is one of the characteristics of TME. As an important antioxidant in cells, GSH can eliminate the generated ROS in some way and weaken the e ciency of CDT [21,22]. These inevitable obstacles imply that the simultaneous introduction of H 2 O 2 supply and GSH elimination functions into a nanoplatform is expected to produce effective CDT.…”

Section: Introductionmentioning

confidence: 99%

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

Zhou

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.

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Nanocatalytic Theranostics with Glutathione Depletion and Enhanced Reactive Oxygen Species Generation for Efficient Cancer Therapy

Cited by 588 publications

References 47 publications

Dual Reactive Oxygen Species Generator Independent of Light and Oxygen for Tumor Imaging and Catalytic Therapy

Dual Reactive Oxygen Species Generator Independent of Light and Oxygen for Tumor Imaging and Catalytic Therapy

Construction of Novel Nanocomposites (Cu-MOF/GOD@HA) for Chemodynamic Therapy

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

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