A carrier-free metal-phenolic network with enhanced ferroptosis-immunotherapy for overcoming tumor resistance and metastasis

Zhang, Ning; Wang, Zijia; Li, Gen; Zhang, Mingzhe; Liu, Quan; Cai, Chunxiu; Shang, Yanfei; Zhu, Hailiang; An, Hailong; Ren, Shenzhen

doi:10.1016/j.cej.2024.150780

Chemical Engineering Journal

2024

DOI: 10.1016/j.cej.2024.150780

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A carrier-free metal-phenolic network with enhanced ferroptosis-immunotherapy for overcoming tumor resistance and metastasis

Ning Zhang,

Zijia Wang,

Gen Li

et al.

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2024

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Self-Healing Photothermal Nanotherapeutics for Enhanced Tumor Therapy through Triple Ferroptosis Amplification and Cascade Inflammation Inhibition

Zheng,

et al. 2024

ACS Appl. Mater. Interfaces

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The therapeutic effectiveness of photothermal therapy (PTT) is limited by heat tolerance and PTT-induced inflammation, which increases the risk of tumor metastasis and recurrence. Ferroptosis combined with PTT can achieve significant therapeutic effects. In this work, we designed self-healing photothermal nanotherapeutics to achieve effective PTT with triple-amplified ferroptosis and cascade inflammation inhibition after photothermal treatment. After the ferroptosis-inducing ability of mangiferin (MF) was first elucidated, the nanocomplex PFeM, coordinated by Fe 3+ and MF with polyvinylpyrrolidone (PVP) modification, was prepared by a one-pot self-assembly method. PFeM with laser irradiation could induce intensified ferroptosis by integrating the functions of MF to deactivate glutathione peroxidase 4, Fe 3+ /Fe 2+ to generate lethal reactive oxygen species via the Fenton reaction, and the photothermal effect to amplify ferroptosis. More importantly, the released MF could achieve cascade inflammation inhibition, thereby reversing the proinflammatory microenvironment caused by PTT. The in vivo antitumor and antiinflammatory effects of PFeM were further confirmed in a 4T1 tumor-bearing mouse model. This study expounding the ferroptosisinducing effects of MF and utilizing the strategy of chelating MF with iron ions can provide a new idea for developing photothermal nanoagents with clinically convertible safety ingredients and a green preparation process that improve efficacy and reduce adverse reactions during PTT.

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Self-Healing Photothermal Nanotherapeutics for Enhanced Tumor Therapy through Triple Ferroptosis Amplification and Cascade Inflammation Inhibition

Zheng,

et al. 2024

ACS Appl. Mater. Interfaces

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Integration of Fe(III)-Chelated Polydopamine and Diallyl Trisulfide for Boosting Ferroptosis to Reverse Multidrug Resistance and Inducing Synergistic Tumor Nanotherapy

Zhao,

Yao,

Huang

et al. 2024

ACS Appl. Nano Mater.

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Multidrug resistance (MDR) has long been a fundamental obstacle in tumor chemotherapy. MDR is often associated with overexpression of an adenosine triphosphate (ATP)-binding cassette transporter in resistant cancer cells, which is highly ATP-dependent. Therefore, reversing MDR by downregulated ATP expression is a promising strategy. This study developed a redoxregulating nanotherapeutic for boosting ferroptosis, reversing MDR, and inducing synergistic tumor therapy. Fe(III)-chelated polydopamine (Fe-PDA) is the key to the design of such a nanotherapeutic, and laser irradiation can speed up the electron transfer between Fe 3+ and Fe 2+ and the production of a hydroxyl radical ( • OH). Coating a layer of Fe-PDA on the surface of mesoporous silica (MSN)-encapsulated diallyl trisulfide (DATS), and the doxorubicin (DOX) was loaded on the surface of Fe-PDA. Upon triggering, the nanotherapeutic (DATS@MSN@Fe-PDA/DOX, DMFPD) produced a photothermal hydroxyl radical ( • OH) and hydrogen sulfide (H 2 S) for apoptotic cell death. The DATS depleted intracellular glutathione (GSH), which together with the produced H 2 S boosted ferroptosis. Ferroptosis and H 2 S effectively caused mitochondrial dysfunction, thereby suppressing the ATP expression. The interactive cell death and chemotherapy sensitization were further demonstrated in a 4T1 tumor-bearing mouse model with a high level of biosafety. This study provides a promising strategy for clinical cancer theragnostics.

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A carrier-free metal-phenolic network with enhanced ferroptosis-immunotherapy for overcoming tumor resistance and metastasis

Cited by 2 publications

References 50 publications

Self-Healing Photothermal Nanotherapeutics for Enhanced Tumor Therapy through Triple Ferroptosis Amplification and Cascade Inflammation Inhibition

Self-Healing Photothermal Nanotherapeutics for Enhanced Tumor Therapy through Triple Ferroptosis Amplification and Cascade Inflammation Inhibition

Integration of Fe(III)-Chelated Polydopamine and Diallyl Trisulfide for Boosting Ferroptosis to Reverse Multidrug Resistance and Inducing Synergistic Tumor Nanotherapy

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