A mitochondria-targeted H2O2/viscosity dual-responsive fluorescent probe for visualizing redox-biophysical remodeling in LPS-induced acute kidney injury

Renal tubular epithelial cells are the primary targets and play a critical role in the pathogenesis of acute kidney injury (AKI). Hydrogen peroxide (H2O2) can induce dynamic changes of oxidative stress, and is considered as a key but not unique marker of AKI. The abnormal microenvironmental of tubular cells, in particular, viscosity, have emerged as a crucial marker of AKI. Therefore, the design of innovative fluorogenic probes for dual-channel imaging H2O2 and viscosity could contribute to a deeper understanding of AKI, as well as aid in the development of early diagnostic and therapeutic strategies. In this work, a near-infrared two-photon fluorescent probe (PB-PB-B(OH)2) was developed, equipped with capable of mitochondria-targeted, dual-responsive of H2O2 and viscosity variations with the same excitation wavelength. In TNF-α induced necroptosis on HK-2 cell models, PB-PB-B(OH)2 demonstrated excellent dual-channel fluorescence response to exogenous H2O2 and evaluated viscosity. In a mouse model of lipopolysaccharide (LPS)-induced AKI, PB-PB-B(OH)2 distinguished between different levels of kidney injury induced by varying injection time of LPS and provided visual evidence of the mitochondrial necroptosis effect. Finally, PB-PB-B(OH)2 was successfully applied to dynamically monitor H2O2 and viscosity levels in the drug-induced AKI therapeutic treatment, revealing a positive correlation between H2O2/viscosity expression and disease progression. These results demonstrate that PB-PB-B(OH)2 is a highly sensitive and selective dual-channel fluorescence probe, suitable for detection of oxidative stress and intracellular microenvironment in vitro and in vivo and is a powerful dynamic monitoring tool for the early diagnosis and mechanistic study of AKI.