Diagnosing Orthotopic Lung Tumor Using a NTR-Activatable Near-Infrared Fluorescent Probe by Tracheal Inhalation

Nitroreductase (NTR) is an enzyme that is upregulated under tumor-depleted oxygen conditions. The majority of studies have been conducted on NTR, but many existing fluorescent imaging tools for monitoring NTR inevitably suffer from weak targeting, low sensitivity, and simple tumor models. Research on diagnosing lung tumors has been very popular in recent years, but targeting assays in orthotopic lung tumors is still of great research value, as such models better mimic the reality of cancer in the organism. Here, we developed a novel near-infrared (NIR) fluorescent probe IR-ABS that jointly targets NTR and carbonic anhydrase IX (CAIX). IR-ABS has excellent sensitivity and selectivity and shows exceptional NTR response in spectroscopic tests. The measurements ensured that this probe has good biosafety in both cells and mice. A better NTR response was found in hypoxic tumor cells at the cellular level, distinguishing tumor cells from normal cells. In vivo experiments demonstrated that IR-ABS achieves a hypoxic response at the zebrafish level and enables rapid and accurate tumor margin distinguishment in different mouse tumor models. More importantly, we successfully applied IR-ABS for NTR detection in orthotopic lung tumor models, further combined with tracheal inhalation drug delivery to improve targeting. To the best of our knowledge, we present for the first time a near-infrared imaging method for targeting lung cancerous tumor in situ via tracheal inhalation drug delivery, in contrast to the reported literature. This NIR fluorescence diagnostic strategy for targeting orthotopic lung cancer holds exciting potential for clinical aid in cancer diagnosis.