Author links open overlay panelJunjie Wang a 1,Rong Yu b 1,Wei Chen c,Xiaomin Ma c,Xingzhou Peng c,Fabiao Yu a,Yongjun Zhu b

• a

• NHC Key Laboratory of Tropical Disease Control, School of Life Science and Medical Technology, Hainan Medical University, Haikou, 571199, China

• b

• Department of Nephrology, Key Laboratory of Emergency and Trauma, Ministry of Education, Key Laboratory of Haikou Trauma, Key Laboratory of Hainan Trauma and Disaster Rescue, The First Affiliated Hospital, Hainan Medical University, Haikou, 571199, China

• c

• School of Biomedical Engineering, Hainan University, Haikou, 570228, China

Received 9 June 2026, Revised 2 July 2026, Accepted 8 July 2026, Available online 10 July 2026, Version of Record 11 July 2026.

Volume 95, September 2026, 104294

https://doi.org/10.1016/j.redox.2026.104294

Highlights

• •A mitochondria-targeted NIR two-photon probe enables H2O2/viscosity dual-channel imaging.

  •Single-wavelength excitation visualizes necroptosis in LPS-induced AKI in vivo.

• •TNF-/LPS-injured HK-2 cells show coupled redox-biophysical remodeling.

• Abstract

  Renal tubular epithelial cells are highly susceptible to mitochondrial dysfunction during acute kidney injury (AKI), in which oxidative stress and microenvironmental remodeling occur before overt functional deterioration. Hydrogen peroxide (H2O2) is an important but nonspecific redox mediator, whereas mitochondrial viscosity provides a complementary biophysical readout associated with organelle stress, protein aggregation, membrane damage, and impaired molecular diffusion. Simultaneous imaging of mitochondrial H2O2 and viscosity may therefore provide a dual-parameter strategy for interrogating redox-biophysical remodeling during AKI-associated tubular injury. Here, we developed a mitochondria-targeted dual-responsive fluorescent probe, PB-PB-B(OH)2, that enables single-excitation dual-channel imaging of H2O2-associated oxidative stress and viscosity-related microenvironmental changes. PB-PB-B(OH)2 showed H2O2-responsive green emission and viscosity-sensitive red emission with limited channel cross-interference under the tested conditions. In HK-2 cells exposed to TNF- or LPS, the probe visualized concurrent increases in mitochondrial oxidative stress-associated green fluorescence and viscosity-related red fluorescence, which were attenuated by NAC or Nec-1s treatment. In an LPS-induced AKI mouse model, PB-PB-B(OH)2 enabled dynamic renal imaging of injury-stage-dependent redox and viscosity changes, which correlated with histological injury, renal function markers, and necroptosis-related signaling proteins. Therapeutic intervention with NAC or Nec-1s reduced both fluorescence signals, supporting the use of this probe for imaging-based monitoring of renal injury progression and treatment response. These results establish PB-PB-B(OH)2 as a mitochondria-targeted dual-parameter molecular imaging tool for visualizing redox-biophysical remodeling in LPS-induced AKI, rather than as a clinically validated replacement for established AKI biomarkers.

• Graphical abstract

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