Photothermal Lysis of Engineered Bacteria to Modulate Amino Acid Metabolism against Tumors

Abstract Bacterial‐mediated synergistic cancer therapy (BMSCT) is used as a promising tumor therapy approach. However, there are some disadvantages of bacterial therapy alone to be resolved, such as low tumor suppression rate in the treatment. In this study, a novel light‐controlled engineered bacterial material which synergistically regulates amino acid metabolism to fight tumors is developed. It transcribes l ‐methionine‐γ‐lyase (MdeA) into Escherichia coli ( E. coli ) and loads the approved photothermal agent indocyanine green (ICG), namely E. coli‐ MdeA@ICG. Using the hypoxic tropism of E. coli , genetically engineered bacteria are first loaded with photothermal agents, then selectively accumulate and replicate in the tumor region. Under laser irradiation, photothermal lysis of E. coli ‐MdeA is performed to release the MdeA and consume the essential amino acid methionine (Met) in the tumor environment. In vitro cell experiments confirm that the E. coli ‐MdeA + NIR group can reach 90% of the 4T1 cells killing. In 4T1 tumor‐bearing mouse models, E. coli ‐MdeA@ICG shows enhanced antitumor efficacy, along with 91.8% of the tumor growth inhibited. Apoptosis of tumor cells is induced under the dual action of photothermal therapy (PTT) and amino acid metabolism therapy. This strategy provides new ideas for the combination of synthetic biology and nanotechnology in anti‐tumor.