Resident macrophages in the tumor microenvironment (TME) generate very low level (&lt; 200 nM) of nitic oxide (NO). NO is implicated in poor clinical prognoses of cancer. We hypothesize that the cause of inflammatory and aggressive tumor types in high-fat diet is due to the steady production of NO. Current technologies for directly monitoring the NO levels suffer from either low resolution (EPR), poor sensitivity (MRI) or invasiveness (amperometry). Although many optical based probes have been developed for sensing NO, most are suitable only for LPS induced NO production where the concentration is in the micromolar range (1000-fold higher than in cancer). Here we have developed the first NIR emitting bioluminescent probe, BL660-NO, with exquisite sensitivity (aided by the lack of autofluorescence from absent incident light) and selectivity for NO. This probe was used to validate our hypothesis at the molecular level. Indeed, our results indicate that inflammatory diet can cause increased NO production through recruitment of macrophages and overproduction of iNOS leading to aggressive tumors.

Development of an activity-based NIR bioluminescent probe for discovery of diet-induced modulation of the tumor microenvironment via nitric oxide

ACS Spring 2022

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