Bimodal Visualization of Mitochondrial Viscosity Remodeling, Morphological Dynamics and Interorganelle Networks in Acute Kidney Injury

The spatiotemporal dynamics of mitochondrial viscosity and its regulatory relationship with organelle interaction networks in cisplatin-induced acute kidney injury (AKI) remain poorly understood, primarily due to the absence of high-precision, multiscale, cross-modal imaging technologies. To overcome this limitation, we pioneered a "trinity" molecular probe design strategy that synergistically integrates electrostatic-driven organelle targeting, microenvironment viscosity-responsive activation, and fluorescence-photoacoustic signal coamplification. Based on this paradigm, we developed ACP, an intelligent dual-modal probe that enables functional spatiotemporal mapping of mitochondrial viscosity dynamics in cisplatin-injured HK-2 cells. Furthermore, we established a sophisticated multiparameter quantitative analysis framework, combining dihedral angle spatial conformation analysis, nanometer-scale organelle membrane distance measurement, and mitochondrial morphometry to systematically decode the dynamic evolution of mitochondrial-lysosomal interaction networks during AKI progression. Therefore, the molecular probe technology and multimodal analytical framework developed in this study may open new avenues for AKI research and pave the way for deeper understanding of organelle-level pathophysiology.