A tumor microenvironment dual responsive contrast agent for contrary contrast-magnetic resonance imaging and specific chemotherapy of tumors

Lu, Yudie; Feng, Jie; Liang, Zhiyu; Lu, Xuanyi; Guo, Shuai; Huang, Lin; Xiong, Wei; Chen, Sijin; Zhou, Huimin; Ma, Xuehua; Xu, Yikai; Qiu, Xiaozhong; Wu, Aiguo; Chen, Xiaoyuan; Shen, Zheyu

doi:10.1039/d1nh00632k

Cited by 13 publications

(7 citation statements)

References 42 publications

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“…These data indicate that AuNP@FeS4 has no significant toxicity to the liver and kidney. No obvious damage is observed in the histological morphology of the major organs, which further indicates that AuNP@FeS4 presents good biological safety during the therapy period (Figure S20). These results indicate that AuNP@FeS4 can significantly inhibit tumor growth and effectively prolong the life span of mice, providing important guidance for further clinical translation of the developed AuNP@FeS4.…”

Section: Resultsmentioning

confidence: 82%

Ultrasmall Self-Cascade AuNP@FeS Nanozyme for H₂S-Amplified Ferroptosis Therapy

Zhan,

Liu,

Yang

et al. 2023

ACS Appl. Mater. Interfaces

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Recently, nanozymes with peroxidase (POD)-like activity have shown great promise for ferroptosis-based tumor therapy, which are capable of transforming hydrogen peroxide (H2O2) to highly toxic hydroxyl radicals (•OH). However, the unsatisfactory therapeutic performance of nanozymes due to insufficient endogenous H2O2 and acidity at tumor sites has always been a conundrum. Herein, an ultrasmall gold (Au) @ ferrous sulfide (FeS) cascade nanozyme (AuNP@FeS) with H2S-releasing ability constructed with an Au nanoparticle (AuNP) and an FeS nanoparticle (FeSNP) is designed to increase the H2O2 level and acidity in tumor cells via the collaboration between cascade reactions of AuNP@FeS and the biological effects of released H2S, achieving enhanced •OH generation as well as effective ferroptosis for tumor therapy. The cascade reaction in tumor cells is activated by the glucose oxidase (GOD)-like activity of AuNP in AuNP@FeS to catalyze intratumoral glucose into H2O2 and gluconic acid; meanwhile, the released H2S from AuNP@FeS reduces H2O2 consumption by inhibiting intracellular catalase (CAT) activity and promotes lactic acid accumulation. The two pathways synergistically boost H2O2 and acidity in tumor cells, thus inducing a cascade to generate abundant •OH by catalyzing H2O2 through the POD-like activity of FeS in AuNP@FeS and ultimately causing amplified ferroptosis. In vitro and in vivo experiments demonstrated that AuNP@FeS presents a superior tumor therapeutic effect compared to that of AuNP or FeS alone. This strategy represents a simple but powerful method to amplify ferroptosis with H2S-releasing cascade nanozymes and will pave a new way for the development of tumor therapy.

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Section: Resultsmentioning

confidence: 82%

Ultrasmall Self-Cascade AuNP@FeS Nanozyme for H₂S-Amplified Ferroptosis Therapy

Zhan,

Liu,

Yang

et al. 2023

ACS Appl. Mater. Interfaces

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“…[43] To disrupt this vicious circle and improve cancer therapeutic efficacy of TNBC, in this study, we propose a strategy with the synergy of ferroptosis, immunosuppression reversal and disulfidptosis. Based on our previous reports on contrary contrast (CC) -magnetic resonance imaging (MRI) [44] and intelligent pore switching hollow mesoporous organosilica nanoparticles (HMON), we also developed an intelligent nanomedicine to realize the TME-responsiveness release of therapeutic agents, effectively instigating a synergistic therapeutic approach leveraging ferroptosis. As shown in Scheme 1A, iron atom (IA) was synthesized in situ in the hollow core of HMON, generating IA@HMON.…”

Section: Introductionmentioning

confidence: 99%

MRI‐Guided Tumor Therapy Based on Synergy of Ferroptosis, Immunosuppression Reversal and Disulfidptosis

Guo,

Li,

Zhou

et al. 2024

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Triple negative breast cancer (TNBC) cells have a high demand for oxygen and glucose to fuel their growth and spread, shaping the tumor microenvironment (TME) that can lead to a weakened immune system by hypoxia and increased risk of metastasis. To disrupt this vicious circle and improve cancer therapeutic efficacy, a strategy is proposed with the synergy of ferroptosis, immunosuppression reversal and disulfidptosis. An intelligent nanomedicine GOx‐IA@HMON@IO is successfully developed to realize this strategy. The Fe release behaviors indicate the glutathione (GSH)‐responsive degradation of HMON. The results of titanium sulfate assay, electron spin resonance (ESR) spectra, 5,5’‐Dithiobis‐(2‐nitrobenzoic acid (DTNB) assay and T1‐weighted magnetic resonance imaging (MRI) demonstrate the mechanism of the intelligent iron atom (IA)‐based cascade reactions for GOx‐IA@HMON@IO, generating robust reactive oxygen species (ROS). The results on cells and mice reinforce the synergistic mechanisms of ferroptosis, immunosuppression reversal and disulfidptosis triggered by the GOx‐IA@HMON@IO with the following steps: 1) GSH peroxidase 4 (GPX4) depletion by disulfidptosis; 2) IA‐based cascade reactions; 3) tumor hypoxia reversal; 4) immunosuppression reversal; 5) GPX4 depletion by immunotherapy. Based on the synergistic mechanisms of ferroptosis, immunosuppression reversal and disulfidptosis, the intelligent nanomedicine GOx‐IA@HMON@IO can be used for MRI‐guided tumor therapy with excellent biocompatibility and safety.

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“…MRI contrast agents (MRICAs) are usually used to improve the distinction between normal and tumor tissues. [6][7][8] MRICAs are developed mainly based on paramagnetic gadolinium (Gd) and manganese complexes that have long electronic relaxation durations and abundant unpaired electrons. 9,10 The Food and Drug Administration (FDA) has approved the use of magnetic iron oxide as a T 2 MRICA; however, gadolinium (Gd)-and manganese (Mn)-based T 1 MRICAs are predominantly used in clinical settings.…”

Section: Introductionmentioning

confidence: 99%

A Targeted Multi-Crystalline Manganese Oxide as a Tumor-Selective Nano-Sized MRI Contrast Agent for Early and Accurate Diagnosis of Tumors

Yang,

Xia,

Dai

et al. 2024

IJN

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Introduction Magnetic resonance imaging (MRI) is an important tool for the accurate diagnosis of malignant tumors in clinical settings. However, the lack of tumor-specific MRI contrast agents limits diagnostic accuracy. Methods Herein, we developed αv integrin receptor-targeting multi-crystalline manganese oxide (MCMO) as a novel MRI contrast agent for accurate diagnosis of tumors by coupling iRGD cyclopeptide PEGylation polymer onto the surface of MCMO (iRGD-pMCMO). Results The MCMO consisted of numerous small crystals and exhibited an oval structure of 200 nm in size. The iRGD-pMCMO actively recognizes tumor cells and effectively accumulates at the tumor site, consequently releasing abundant Mn 2+ ions in a weakly acidic and high-GSH-expressing tumor microenvironment. Subsequently, Mn 2+ ions interact with cellular GSH to form Mn-GSH chelates, enabling efficient T 1 -weighted MR contrast imaging. In vivo experiments indicated that iRGD-pMCMO significantly improved T 1 -weighted images, achieving an accurate diagnosis of subcutaneous and orthotopic tumors. The results verified that the T 1 contrast effect of iRGD-pMCMO was closely associated with the expression of GSH in tumor cells. Conclusion Altogether, the novel tumor-targeting, highly sensitive MRI contrast agent developed in this study can improve the accuracy of MRI for tumor diagnosis.

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A tumor microenvironment dual responsive contrast agent for contrary contrast-magnetic resonance imaging and specific chemotherapy of tumors

Abstract: Development of Magnetic Resonance Imaging (MRI) contrast agents (CAs) is still one of the research hotspots due to the inherent limitations of T1- or T2- weighted CAs, and T1/T2 dual-mode...

Cited by 13 publications

References 42 publications

Ultrasmall Self-Cascade AuNP@FeS Nanozyme for H₂S-Amplified Ferroptosis Therapy

Ultrasmall Self-Cascade AuNP@FeS Nanozyme for H₂S-Amplified Ferroptosis Therapy

MRI‐Guided Tumor Therapy Based on Synergy of Ferroptosis, Immunosuppression Reversal and Disulfidptosis

A Targeted Multi-Crystalline Manganese Oxide as a Tumor-Selective Nano-Sized MRI Contrast Agent for Early and Accurate Diagnosis of Tumors

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A tumor microenvironment dual responsive contrast agent for contrary contrast-magnetic resonance imaging and specific chemotherapy of tumors

Abstract: Development of Magnetic Resonance Imaging (MRI) contrast agents (CAs) is still one of the research hotspots due to the inherent limitations of T1- or T2- weighted CAs, and T1/T2 dual-mode...

Cited by 13 publications

References 42 publications

Ultrasmall Self-Cascade AuNP@FeS Nanozyme for H2S-Amplified Ferroptosis Therapy

Ultrasmall Self-Cascade AuNP@FeS Nanozyme for H2S-Amplified Ferroptosis Therapy

MRI‐Guided Tumor Therapy Based on Synergy of Ferroptosis, Immunosuppression Reversal and Disulfidptosis

A Targeted Multi-Crystalline Manganese Oxide as a Tumor-Selective Nano-Sized MRI Contrast Agent for Early and Accurate Diagnosis of Tumors

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Ultrasmall Self-Cascade AuNP@FeS Nanozyme for H₂S-Amplified Ferroptosis Therapy

Ultrasmall Self-Cascade AuNP@FeS Nanozyme for H₂S-Amplified Ferroptosis Therapy