Intracellular self-aggregation of biomimetic Fe<sub>3</sub>O<sub>4</sub> nanoparticles for enhanced ferroptosis-inducing therapy of breast cancer

Zhang, Zhendong; Xie, Beibei; Lu, Xiaojie; Xiong, Lishan; Li, Xinyuan; Zhang, Yan; Li, Chunlai; Wang, Chenhui

doi:10.1039/d3nr04305c

“…Studies have shown that in the treatment of human fibrosarcoma, SAS can inhibit the expression of system Xc on the fibrosarcoma cell membrane, suggesting that SAS can inhibit the occurrence and development of tumors to a certain extent. The possible mechanism by which SAS induces ferroptosis is by interrupting the cystine uptake signaling pathway [29][30][31][32][33][34][35][36][37][38] . System Xc¯ is one of the key signal pathways of ferroptosis.…”

Section: Discussionmentioning

confidence: 99%

Effect of sulfasalazine on ferroptosis during intestinal injury in rats after liver transplantation

Wu,

Bu,

Tan

et al. 2024

Sci Rep

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Using a rat autologous orthotopic liver transplantation (AOLT) model and liver cold ischemia–reperfusion (I/R)-induced intestinal injury, we clarified whether ferroptosis occurred in rat AOLT cold I/R-induced intestinal injury. Additionally, the role and possible mechanism of the ferroptosis activator sulfasalazine (SAS) in intestinal injury-induced ferroptosis in rats with AOLT liver cold I/R were investigated. Sixty specific pathogen free (SPF)-grade adult male Sprague‒Dawley (SD) rats were randomly divided into 5 groups using the random number table method (n = 12). Six rats were randomly selected at 6 hour (h) and 24 h after I/R. Inferior vena cava blood specimens were collected from the portal vein (PV) opening at 6 h and 24 h. The concentrations of serum malondialdehyde (MDA), serum interleukin 6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA). Ileal tissue was obtained from the PV opening in rats in each group at 6 h and 24 h, and ileal tissue sections were observed under light microscopy. The contents of intestinal MDA, superoxide dismutase (SOD), glutathione(GSH), glutathione peroxidase 4 (GPX4), and tissue iron were determined by ELISA, and the expression of GPX4 and the cysteine glutamate reverse transporter light chain protein (xCT) was determined by Western blot. The experimental results show that ferroptosis is involved in the pathophysiological process of intestinal injury induced by cold hepatic ischemia–reperfusion in AOLT rats. In addition, SAS (500 mg/kg) may inhibit the cystine/glutamate antiporters (System Xc¯)/GSH/GPX4 signal axis in intestinal injury induced by cold I/R in rat AOLT liver, or iron overload after reperfusion, causing a massive accumulation of L-ROS and activating cellular ferroptosis, further aggravate the intestinal injury.

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“…Researchers have created self-aggregating Fe 3 O 4 nanomaterials within tumor cells, prolonging the residence time to enhance ROS production and achieve a better ferroptosis therapy effect. [13] The scarcity of Fe 3 O 4 nanomaterials reported in the literature to enhance tumor cell ferroptosis efficacy necessitates the development of new strategies for Fe 3 O 4 nanomaterials to achieve a higher degree of ferroptosis therapy enhancement, combining it with immunotherapy for more efficient tumor growth suppression.…”

Section: Introductionmentioning

confidence: 99%

Monitoring ROS Responsive Fe₃O₄‐based Nanoparticle Mediated Ferroptosis and Immunotherapy via ¹²⁹Xe MRI

Zhang,

Qiu,

Wang

et al. 2024

Angewandte Chemie

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The immune checkpoint blockade strategy has improved the survival rate of late‐stage lung cancer patients. However, the low immune response rate limits the immunotherapy efficiency. Here, we report a ROS‐responsive Fe3O4‐based nanoparticle that undergoes charge reversal and disassembly in the tumor microenvironment, enhancing the uptake of Fe3O4 by tumor cells and triggering a more severe ferroptosis. In the tumor microenvironment, the nanoparticle rapidly disassembles and releases the loaded GOx and the immune‐activating peptide Tuftsin under overexpressed H2O2. GOx can consume the glucose of tumor cells and generate more H2O2, promoting the disassembly of the nanoparticle and drug release, thereby enhancing the therapeutic effect of ferroptosis. Combined with Tuftsin, it can more effectively reverse the immune‐suppressive microenvironment and promote the recruitment of effector T cells in tumor tissues. Ultimately, in combination with α‐PD‐L1, there is significant inhibition of the growth of lung metastases. Additionally, the hyperpolarized 129Xe method has been used to evaluate the Fe3O4 nanoparticle‐mediated immunotherapy, where the ventilation defects in lung metastases have been significantly improved with complete lung structure and function recovered. The ferroptosis‐enhanced immunotherapy combined with non‐radiation evaluation methodology paves a new way for designing novel theranostic agents for cancer therapy.

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Monitoring ROS Responsive Fe₃O₄‐based Nanoparticle Mediated Ferroptosis and Immunotherapy via ¹²⁹Xe MRI

Zhang,

Qiu,

Wang

et al. 2024

Angew Chem Int Ed

2

0

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The immune checkpoint blockade strategy has improved the survival rate of late‐stage lung cancer patients. However, the low immune response rate limits the immunotherapy efficiency. Here, we report a ROS‐responsive Fe3O4‐based nanoparticle that undergoes charge reversal and disassembly in the tumor microenvironment, enhancing the uptake of Fe3O4 by tumor cells and triggering a more severe ferroptosis. In the tumor microenvironment, the nanoparticle rapidly disassembles and releases the loaded GOx and the immune‐activating peptide Tuftsin under overexpressed H2O2. GOx can consume the glucose of tumor cells and generate more H2O2, promoting the disassembly of the nanoparticle and drug release, thereby enhancing the therapeutic effect of ferroptosis. Combined with Tuftsin, it can more effectively reverse the immune‐suppressive microenvironment and promote the recruitment of effector T cells in tumor tissues. Ultimately, in combination with α‐PD‐L1, there is significant inhibition of the growth of lung metastases. Additionally, the hyperpolarized 129Xe method has been used to evaluate the Fe3O4 nanoparticle‐mediated immunotherapy, where the ventilation defects in lung metastases have been significantly improved with complete lung structure and function recovered. The ferroptosis‐enhanced immunotherapy combined with non‐radiation evaluation methodology paves a new way for designing novel theranostic agents for cancer therapy.

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Intracellular self-aggregation of biomimetic Fe₃O₄ nanoparticles for enhanced ferroptosis-inducing therapy of breast cancer

Abstract: A supramolecular and cell membrane co-modified drug delivery system was constructed to enhance Fe3O4 and SAS synergistically induced ferroptosis anti-tumor therapy.

Cited by 3 publications

References 38 publications

Effect of sulfasalazine on ferroptosis during intestinal injury in rats after liver transplantation

Effect of sulfasalazine on ferroptosis during intestinal injury in rats after liver transplantation

Monitoring ROS Responsive Fe₃O₄‐based Nanoparticle Mediated Ferroptosis and Immunotherapy via ¹²⁹Xe MRI

Monitoring ROS Responsive Fe₃O₄‐based Nanoparticle Mediated Ferroptosis and Immunotherapy via ¹²⁹Xe MRI

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Intracellular self-aggregation of biomimetic Fe3O4 nanoparticles for enhanced ferroptosis-inducing therapy of breast cancer

Abstract: A supramolecular and cell membrane co-modified drug delivery system was constructed to enhance Fe3O4 and SAS synergistically induced ferroptosis anti-tumor therapy.

Cited by 3 publications

References 38 publications

Effect of sulfasalazine on ferroptosis during intestinal injury in rats after liver transplantation

Effect of sulfasalazine on ferroptosis during intestinal injury in rats after liver transplantation

Monitoring ROS Responsive Fe3O4‐based Nanoparticle Mediated Ferroptosis and Immunotherapy via 129Xe MRI

Monitoring ROS Responsive Fe3O4‐based Nanoparticle Mediated Ferroptosis and Immunotherapy via 129Xe MRI

Contact Info

Product

Resources

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Intracellular self-aggregation of biomimetic Fe₃O₄ nanoparticles for enhanced ferroptosis-inducing therapy of breast cancer

Monitoring ROS Responsive Fe₃O₄‐based Nanoparticle Mediated Ferroptosis and Immunotherapy via ¹²⁹Xe MRI

Monitoring ROS Responsive Fe₃O₄‐based Nanoparticle Mediated Ferroptosis and Immunotherapy via ¹²⁹Xe MRI