Iron-based nanoparticles for MR imaging-guided ferroptosis in combination with photodynamic therapy to enhance cancer treatment

Chen, Qifang; Ma, Xianbin; Xie, Li; Chen, Wenjie; Xu, Zhigang; Song, Erqun; Zhu, Xiaolin; Song, Yang

doi:10.1039/d0nr08757b

Cited by 107 publications

(71 citation statements)

References 58 publications

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“…In another study, in which ultrasmall CaO 2 and Fe 3 O 4 were co-loaded on to dendritic mesoporous silica NPs, researchers showed that these particles can achieve tumor specialized localization and induction of Fenton reaction, thus triggering ferroptosis ( Li and Rong, 2020 ). The Fe 3 O 4 -PLGA-Ce 6 nanosystem, which dissociates in acidic TME, and the Fe 2+ -based metal–organic framework, which delivers Fe 2+ to cancer cells, can also promote the Fenton reaction and facilitate ferroptosis ( Xu et al, 2020b ; Chen Q. et al, 2021 ).…”

Section: Ferroptosis and The Tumor Microenvironmentmentioning

confidence: 99%

Ferroptosis and Cancer: Complex Relationship and Potential Application of Exosomes

Liu

et al. 2021

Front. Cell Dev. Biol.

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Cell death induction has become popular as a novel cancer treatment. Ferroptosis, a newly discovered form of cell death, features regulated, iron-dependent accumulation of lipid hydroperoxides. Since this word “ferroptosis” was coined, numerous studies have examined the complex relationship between ferroptosis and cancer. Here, starting from the intrinsic hallmarks of cancer and cell death, we discuss the theoretical basis of cell death induction as a cancer treatment. We review various aspects of the relationship between ferroptosis and cancer, including the genetic basis, epigenetic modification, cancer stem cells, and the tumor microenvironment, to provide information and support for further research on ferroptosis. We also note that exosomes can be applied in ferroptosis-based therapy. These extracellular vesicles can deliver different molecules to modulate cancer cells and cell death pathways. Using exosomes to control ferroptosis occurring in targeted cells is promising for cancer therapy.

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Section: Ferroptosis and The Tumor Microenvironmentmentioning

confidence: 99%

Ferroptosis and Cancer: Complex Relationship and Potential Application of Exosomes

Liu

et al. 2021

Front. Cell Dev. Biol.

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“…Recently discovered ferroptosis-inducing agents mainly include iron-based materials (e.g. inorganic iron-involved nanoparticles (NPs), Fe-metal–organic frameworks (Fe-MOFs), iron storage or transport proteins) [ 1 , 3 , 20 , 24 – 26 ] and certain small molecule drugs (e.g. sorafenib (SRF), erastin, sulfasalazine, artemisinin) [ 23 , 27 – 29 ], the former accelerating iron-catalyzed ROS production and the latter inhibiting GSH biosynthesis and then decreasing glutathione peroxidase 4 (GPX4, the lipid repair enzyme) expression, eventually leading to large amounts of intracellular LPO accumulation.…”

Section: Introductionmentioning

confidence: 99%

“…Nanoparticle (NP) platforms offer an unmatched potential for tumor-targeting simultaneous delivery of PS, exogenous iron and small GSH/GPX4 reduction molecule [ 30 – 32 ]. Recently, several Fe-MOFs or Fe-based inorganic NPs have been emerged for PDT and ferroptosis combining therapy, achieving significantly enhanced therapeutic outcomes in tumor oxidation treatments [ 11 , 20 , 26 – 29 ], however, the biocompatibility, tumor-targeting capacity and clinical translation prospect of which still exist great concerns. Additionally, these nanosystems utilized the acid condition or high concentration of matrix metalloproteinase (MMP) of TME to trigger cargo release, but these differentiations between normal tissues and tumor tissues are not significant enough and easily be affected by the tumor heterogeneity [ 33 – 35 ].…”

Section: Introductionmentioning

confidence: 99%

Hypoxia-responsive nanoreactors based on self-enhanced photodynamic sensitization and triggered ferroptosis for cancer synergistic therapy

Wang

Zhang

et al. 2021

J Nanobiotechnol

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Background Photodynamic therapy (PDT), a typical reactive oxygen species (ROS)-dependent treatment with high controllability, has emerged as an alternative cancer therapy modality but its therapeutic efficacy is still unsatisfactory due to the limited light penetration and constant oxygen consumption. With the development of another ROS-dependent paradigm ferroptosis, several efforts have been made to conquer the poor efficacy by combining these two approaches; however the biocompatibility, tumor-targeting capacity and clinical translation prospect of current studies still exist great concerns. Herein, a novel hypoxia-responsive nanoreactor BCFe@SRF with sorafenib (SRF) loaded inside, constructed by covalently connecting chlorin e6 conjugated bovine serum albumin (BSA-Ce6) and ferritin through azobenzene (Azo) linker, were prepared to offer unmatched opportunities for high-efficient PDT and ferroptosis synergistic therapy. Results The designed BCFe@SRF exhibited appropriate size distribution, stable dispersity, excellent ROS generation property, controllable drug release capacity, tumor accumulation ability, and outstanding biocompatibility. Importantly, the BCFe@SRF could be degraded under hypoxia environment to release BSA-Ce6 for laser-triggered PDT, ferritin for iron-catalyzed Fenton reaction and SRF for tumor antioxidative defense disruption. Meanwhile, besides PDT effects, it was found that BCFe@SRF mediated treatment upon laser irradiation in hypoxic environment not only could accelerate lipid peroxidation (LPO) generation but also could deplete intracellular glutathione (GSH) and decrease glutathione peroxidase (GPX4) expression, which was believed as three symbolic events during ferroptosis. All in all, the BCFe@SRF nanoreactor, employing multiple cascaded pathways to promote intracellular ROS accumulation, presented remarkably outstanding antitumor effects both in vitro and in vivo. Conclusion BCFe@SRF could serve as a promising candidate for synergistic PDT and ferroptosis therapy, which is applicable to boost oxidative damage within tumor site and will be informative to future design of ROS-dependent therapeutic nanoplatforms. Graphic abstract

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“…According to the speci c coordination properties between introduced Fe 2+ /Fe 3+ with Fe-coordination proteins, doping biocompatible Fe 2+ /Fe 3+ into silica framework (Fe-HMON NPs) could further improve its biodegradability [36]. However, traditional iron delivery nanomaterials usually exhibit nonspeci c effects, which are mainly delivered through enhanced permeability and retention effects may cause signi cant side effects when applied in vivo [37]. Transferrin is an endogenous protein that can transport Fe 3+ to cells with overexpression of the transferrin receptor [38].…”

Section: Introductionmentioning

confidence: 99%

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

Zhou

et al. 2021

Preprint

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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.

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Iron-based nanoparticles for MR imaging-guided ferroptosis in combination with photodynamic therapy to enhance cancer treatment

Abstract: Ferroptosis therapy, which applies ferroptotic inducers to produce lethal lipid peroxidation and induce the death of tumor cells, is regarded as a promising therapeutic strategy for cancer treatment. However, there...

Cited by 107 publications

References 58 publications

Ferroptosis and Cancer: Complex Relationship and Potential Application of Exosomes

Ferroptosis and Cancer: Complex Relationship and Potential Application of Exosomes

Hypoxia-responsive nanoreactors based on self-enhanced photodynamic sensitization and triggered ferroptosis for cancer synergistic therapy

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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