Background-suppressed tumor-targeted photoacoustic imaging using bacterial carriers

Photoacoustic (PA) imaging offers promise for biomedical applications due to its ability to image deep within biological tissues while providing detailed molecular information; however, its detection sensitivity is limited by high background signals that arise from endogenous chromophores. Genetic reporter proteins with photoswitchable properties enable the removal of background signals through the subtraction of PA images for each light-absorbing form. Unfortunately, the application of photoswitchable chromoproteins for tumor-targeted imaging has been hampered by the lack of an effective targeted delivery scheme; that is, photoswitchable probes must be delivered in vivo with high targeting efficiency and specificity. To overcome this limitation, we have developed a tumor-targeting delivery system in which tumor-homing bacteria (Escherichia coli) are exploited as carriers to affect the point-specific delivery of genetically encoded photochromic probes to the tumor area. To improve the efficiency of the desired background suppression, we engineered a phytochrome-based reporter protein (mDrBphP-PCMm/F469W) that displays higher photoswitching contrast than those in the current state of the art. Photoacoustic computed tomography was applied to achieve good depth and resolution in the context of in vivo (mice) imaging. The present system effectively integrates a genetically encoded phytochrome-based reporter protein, PA imaging, and synthetic biology (GPS), to achieve essentially background-suppressed tumor-targeted PA monitoring in deepseated tissues. The ability to image tumors at substantial depths may enable target-specific cancer diagnoses to be made with greater sensitivity, fidelity, and specificity.

Automated summary

This study developed a tumor-targeting delivery system using tumor-homing bacteria as carriers to deliver genetically encoded photochromic probes to the tumor area in order to eliminate background signals in photoacoustic imaging. The system integrated a genetically encoded reporter protein, photoacoustic imaging, and synthetic biology to achieve background-suppressed tumor-targeted imaging in deep-seated tissues, enabling more sensitive, accurate, and specific cancer diagnoses.