Specific Lung-Targeting Shortwave Infrared Luminescence Nanoprobe: Precisely Delineating Sepsis-Induced Acute Lung Injury

Sepsis-induced acute lung injury (ALI), a life-threatening condition, necessitates a deeper molecular-level understanding to promote the development of therapeutic strategies. Although hydrogen sulfide (H₂S) has been implicated in sepsis-associated ALI, current detection methods and poor pulmonary targeting have limited mechanistic insights. In this study, we present a lung-targeted shortwave infrared (SWIR) nanoprobe (RENPs@PB@LIP) for noninvasive monitoring of H₂S in ALI though a novel mismatched resonance energy transfer (MRET) strategy. Specifically, the emission around 1475 nm from Tm³⁺-doped rare-earth doped nanoparticles (RENPs) can be quenched by Prussian blue (PB), which absorbs light in the 600-900 nm range, via modulating the shared energy level of the emissions at 1475 and 812 nm. This energy modulation allows for the detection of H₂S through PB degradation upon reaction. Additionally, positively charged liposomes encapsulate the nanoprobe, promoting its preferential accumulation in the lungs over the liver. Our system enables timely, noninvasive monitoring of H₂S levels in the lungs and facilitates the assessment of ALI progression and prognosis <i>in vivo</i>. This approach holds significant potential for elucidating the pathogenesis of ALI and guiding therapeutic interventions.