Exploiting metabolic vulnerabilities through synergistic ferroptosis and disulfidptosis for breast cancer therapy DOI Creative Commons
Yu Liang,

Hekui Lan,

Qiuyu Li

и другие.

Journal of Advanced Research, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Ferroptosis represents a promising therapeutic approach for breast cancer treatment. However, cells can develop resistance through the SLC7A11-GSH-GPX4 axis, wherein increased SLC7A11 expression enhances cystine uptake, replenishes GSH, and reactivates GPX4. Notably, with high become vulnerable to disulfidptosis under glucose-deprived conditions. We aimed dual-mode strategy that simultaneously induces ferroptosis by targeting both lipid peroxidation glucose metabolism in cells. Fe-Cu-SS metal-organic frameworks (MOFs) loaded BAY876 (FCSP@876 MOFs) were synthesized enhance trigger The MOFs characterized using transmission electron microscopy (TEM), Fourier-transform infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), UV-Vis spectroscopy. In vitro experiments demonstrated FCSP@876 reactive oxygen species (ROS) levels while depleting NADPH. Western blotting actin filament staining confirmed underlying mechanisms. vivo xenograft BALB/c mice assessed synergistic effects of induction. During induction, exhibited an adaptive upregulation expression. effectively counteracted this mechanism inducing restricting uptake BAY876, leading NADPH depletion subsequent disulfidptosis. Both enhanced efficacy compared single-mode treatments. This study successfully developed novel combines MOFs, offering overcoming therapy.

Язык: Английский

Exploiting metabolic vulnerabilities through synergistic ferroptosis and disulfidptosis for breast cancer therapy DOI Creative Commons
Yu Liang,

Hekui Lan,

Qiuyu Li

и другие.

Journal of Advanced Research, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Ferroptosis represents a promising therapeutic approach for breast cancer treatment. However, cells can develop resistance through the SLC7A11-GSH-GPX4 axis, wherein increased SLC7A11 expression enhances cystine uptake, replenishes GSH, and reactivates GPX4. Notably, with high become vulnerable to disulfidptosis under glucose-deprived conditions. We aimed dual-mode strategy that simultaneously induces ferroptosis by targeting both lipid peroxidation glucose metabolism in cells. Fe-Cu-SS metal-organic frameworks (MOFs) loaded BAY876 (FCSP@876 MOFs) were synthesized enhance trigger The MOFs characterized using transmission electron microscopy (TEM), Fourier-transform infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), UV-Vis spectroscopy. In vitro experiments demonstrated FCSP@876 reactive oxygen species (ROS) levels while depleting NADPH. Western blotting actin filament staining confirmed underlying mechanisms. vivo xenograft BALB/c mice assessed synergistic effects of induction. During induction, exhibited an adaptive upregulation expression. effectively counteracted this mechanism inducing restricting uptake BAY876, leading NADPH depletion subsequent disulfidptosis. Both enhanced efficacy compared single-mode treatments. This study successfully developed novel combines MOFs, offering overcoming therapy.

Язык: Английский

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