Work

MHY@MO@PPP inhibits ferroptosis positive feedback and delays the acute kidney injury-to-chronic kidney disease transition by remodeling the Fe2+-mTORC1-GPX4 axis

Year: 2026

Type: article

Abstract: AKI-to-CKD progression is shaped by sustained tubular stress, ferroptosis-related iron imbalance, and oxidative injury. To target this process, we developed an MHY1485-loaded molybdenum oxide (MoOx) nanozyme coated with a pH-responsive phenylboronic acid-polyethylene glycol-phenylboronic acid (PBA-PEG-PBA) polymer (MHY@MO@PPP). We tested whether this platform could weaken the ferroptosis-associated injury loop and delay AKI-to-CKD transition through regulation of the Fe 2+ -mechanistic target of rapamycin complex 1 (mTORC1)-glutathione peroxidase 4 (GPX4) axis. Material properties were examined by dynamic light scattering (DLS), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Biological activity was assessed in erastin-induced ferroptotic human renal proximal tubular epithelial (HK-2) cells and in a C57BL/6 mouse unilateral ischemia-reperfusion injury (UIRI) model. MHY@MO@PPP showed stimulus-responsive MHY1485 release under simulated lesion-like conditions, lowered reactive oxygen species (ROS), lipid peroxidation, and free Fe 2+ , restored mitochondrial function, and improved cell survival. Mechanistic assays showed increased p-mTOR and GPX4 expression with reduced autophagy-related stress, supporting attenuation of the ferroptosis-related feedback state. Proteomic analysis and functional intervention experiments further implicated the Fe 2+ -mTORC1-GPX4 axis in the protective response. In vivo, MHY@MO@PPP improved renal function and reduced renal tissue injury and fibrosis. These findings support a nanozyme-based strategy that combines catalytic redox regulation with pathway modulation to mitigate AKI-to-CKD progression.

Source: Journal of Nanobiotechnology

DOI: 10.1186/s12951-026-04918-w

Authors: Chenhao Li, Chao Zhang, Chuanqi Zhang, Shiyu Duan, Jiali Zhang, Hongyue Wang

Institutions: Jilin University, First Hospital of Jilin University

Language: English

Topic: Ferroptosis and cancer prognosis

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,790