Background-suppressed tumor-targeted photoacoustic imaging using bacterial carriers

Significance Photoacoustic (PA) imaging can provide information about deep-seated biological tissues. Unfortunately, signal intensity and resolution can be limited by background signals arising from endogenous chromophores. Photochromism, the use of agents that go from colorless to colored, has been suggested to be a promising avenue to overcome this limitation. However, a viable method that allows practical applications of this so-called background-suppressed PA imaging is still lacking. Here, we report the engineering of a phytochrome-based reporter protein (m Dr BphP-PCMm/F469W) that displays high photoswitching contrast. Its expression in Escherichia coli enables point-specific imaging within the tumor region over several days and permits PA monitoring of deep-seated tumor tissues via reduction of background signals.