Bimodal Imaging of Tumors via Genetically Engineered Escherichia coli

Although there are emerging innovations of molecular imaging probes to detect and image tumors, most of these molecular dyes and nanoparticles have limitations of low targetability in tumors and fast clearance when administered systemically. In contrast, some bacteria, such as Escherichia coli MG1655, can selectively proliferate in a hypoxic environment inside of a tumor for several days, which highlights the potential for the development of a genetically encoded multimodal imaging probe to monitor the progress of the tumor. Here, we developed bimodal imaging tumor-homing bacteria (GVs-miRFP680 MG1655) that allow both optical and acoustic imaging in tumor-bearing mice. An in vivo optical image system and a Vevo 2100 imaging system were applied to detect different imaging properties of the engineered bacteria in vivo. Our results show that the GVs-miRFP680 MG1655 bacteria can effectively integrate the advantages of low tissue absorbance from near-infrared fluorescent proteins and non-invasiveness from gas vesicles. We successfully developed GVs-miRFP680 MG1655 bacteria, which have both acoustic and optical imaging abilities in vitro and in vivo. The acoustic signal can last for up to 25 min, while the near-infrared fluorescence signal can last for up to 96 h. The combination of different imaging modalities in the tumor-homing bacteria may contribute to the non-invasive monitoring of the therapeutic effect of bacterial therapy in the future.