Classification of pulmonary inflammation stages and assessment of multicomponent drug intervention based on spatiotemporal imaging variations utilizing RhB-conjugated poly-L-lysine nanoparticles

Acute pulmonary inflammation, a major cause of morbidity and mortality, involves complex immune responses and increased vascular permeability. Conventional imaging techniques for assessing pneumonia and monitoring vascular leakage have limitations in spatial resolution and practicality. Rhodamine B-conjugated poly-L-lysine (RhB-PLL) self-assembled nanoparticles (NPs) were synthesized for targeting mitochondria and sensing vascular permeability. Dynamic spatiotemporal imaging analysis stratifies the progression of acute pneumonia into four distinct stages. Six phosphatidylcholine metabolites, exhibiting stage-dependent variations, were proposed as potential biomarkers to support RhB-PLL detection. Subsequently, Fuzheng Jiedu decoction (FZJD) was used as a model to validate the rationale of syndrome-specific treatment for pneumonia. Three simplified prescriptions derived from FZJD showed unique advantages at different stages. Xiaochaihu decoction (XCH) relieved inflammation and oxidative stress in mild to moderate cases; Sanren decoction (SR) reduced vascular leakage and prevented pulmonary edema in moderate to severe cases; Maxingshigan decoction (MXSG) improved mitochondrial function, prevented microcirculatory disorders in severe to critical cases. The combined prescription, FZJD, mitigated disease progression in mild to moderate cases and demonstrated the benefits of overall intervention. This conclusion was further substantiated by metabolomics cluster analysis. Real-time RhB-PLL multimodal imaging enables precise visualization and detection of inflammation progress, facilitates therapy assessment, and enhances the understanding of multicomponent drug combinations. • Novel RhB-PLL nanoparticles act as bifunctional probes for real-time imaging of mitochondrial dysfunction & vascular permeability in pneumonia. • RhB-PLL imaging stratifies acute pneumonia progression into four distinct stages. • RhB-PLL nanoparticles enable TCM multicomponent drug intervention assessment in pneumonia.