In vivo monitoring of theranostic fluorescence bacteria in orthotopic colon cancer model with multiscale fluorescence endoscopy

摘要

Bacteria-mediated cancer imaging and immunotherapy is emerging fields. However, most of the study related totargeting and monitoring of therapeutic response after bacterial therapy was done with tissue analysis after sacrificed theanimal. To evaluate the theranostic efficacy of fluorescence encoded bacteria in vivo, the tumor should be made on thesubcutaneous area due to the limitation of light penetration of the tissue material. However, the subcutaneous xenograftmodel doesn’t reflect the actual tumor microenvironment. In this study, we monitored theranostic bacteria in orthotopictumor model with lab-built wide-field fluorescence endoscopy (WFE) and commercialized confocal endomicroscopy(CFEM) in vivo. First, orthotopic mouse colon cancer models were made by using endoscopic cancer cell implantationmethods. Seconds, fluorescence emitting theranostic bacteria was constructed by using Salmonella strain. The bacteriawere injected into the orthotopic colon tumor-bearing mice via tail vein injection. Finally, we serially monitoredfluorescence signal emitted from theranostic bacteria with WFE and CFEM. Multiscale fluorescence image showed theaccumulation of bacteria within the tumor area compared to normal tissue contrast. We expected that this endoscopicfluorescence imaging approaches can be used in the direct monitoring of bacterial immunotherapy in vivo.