Reporter gene-based optoacoustic imaging of E. coli targeted colon cancer in vivo

Abstract

Bacteria-mediated cancer-targeted therapy is a novel experimental strategy for the treatment of cancers. Bacteria can be engineered to overcome a major challenge of existing therapeutics by differentiating between malignant and healthy tissue. A prerequisite for further development and study of engineered bacteria is a suitable imaging concept which allows bacterial visualization in tissue and monitoring bacterial targeting and proliferation. Optoacoustics (OA) is an evolving technology allowing whole-tumor imaging and thereby direct observation of bacterial colonization in tumor regions. However, bacterial detection using OA is currently hampered by the lack of endogenous contrast or suitable transgene fluorescent labels. Here, we demonstrate improved visualization of cancer-targeting bacteria using OA imaging and E. coli engineered to express tyrosinase, which uses L-tyrosine as the substrate to produce the strong optoacoustic probe melanin in the tumor microenvironment. Tumors of animals injected with tyrosinase-expressing E. coli showed strong melanin signals, allowing to resolve bacterial growth in the tumor over time using multispectral OA tomography (MSOT). MSOT imaging of melanin accumulation in tumors was confirmed by melanin and E. coli staining. Our results demonstrate that using tyrosinase-expressing E. coli enables non-invasive, longitudinal monitoring of bacterial targeting and proliferation in cancer using MSOT.

Bacterial‐Mediated Tumor Therapy: Old Treatment in a New Context

“…[ 204 ] Optical imaging techniques based on bacteria‐mediated bioluminescence and fluorescence can not only detect successful bacteria localization in tumors to predict their proliferation, but also improve the diagnosis and treatment of cancers. [ 20 ] For example, E. coli MG1655 engineered to express tyrosinase, which uses l ‐tyrosine as the substrate to produce the strong optoacoustic probe melanin [ 205 ] or carried 18 F‐FDS PET to visualize CT‐26 tumor in mouse model. [ 20b ] S. typhimurium have also been engineered to express bacterial luciferase gene lux, [ 112a ] RLuc8, [ 187b ] or GFP [ 110 , 111 , 112 ] for visualization of tumor distribution.…”

Optical Resolution Photoacoustic Microscopy Imaging in the Detection of Early Oral Cancer under Image Reconstruction Algorithm

“…Different from the traditional dual-modality imaging system, this system uses weak coherent light in the optical coherence tomography system to detect photoacoustic signals, which gets rid of the limitation of using piezoelectric ceramic ultrasonic detectors to detect photoacoustic signals and improves the sensitivity of the system [21]. In addition to performing conventional optical resolution photoacoustic microscopy imaging experiments, an image processing algorithm can extract parameters such as blood vessel diameter, total blood vessel length, and blood vessel density of the complex capillary network in the image [22]. In this research, the principle of annular array PAT in two-dimensional space was introduced in detail, and the generation, propagation, sampling, and reconstruction process of photoacoustic signal were analyzed and sorted out from the perspective of physical principle and mathematical equations.…”

Seed-Mediated Galvanic Synthesis of CuS–Au Nanohybrids for Photo-Theranostic Applications

“…15 Understanding the demand for molecular PA imaging, PA probes have also been explored to achieve targeted immunotherapy 16 and bacteriamediated cancer therapy serving as molecular PA contrast agents. 17,18 In addition, PA spectroscopy (PAS) is widely used to study the composition of mixtures, functionalities, and improved detection sensitivities. 19 Moreover, the PTT agents can also serve as exogenous contrast agents for PAI, enabling light-based theranostics.…”

“…PAI also uses exogenous contrast agents such as organic dyes, nanoparticles, engineered bacterial vesicles, and so on, allowing for improved detection and characterization of lesions or other structures of interest. , In the past few years, several PA probes have been synthesized using different methodologies for various tissue-targeting applications . Understanding the demand for molecular PA imaging, PA probes have also been explored to achieve targeted immunotherapy and bacteria-mediated cancer therapy serving as molecular PA contrast agents. , In addition, PA spectroscopy (PAS) is widely used to study the composition of mixtures, functionalities, and improved detection sensitivities …”