Photothermal Lysis Of Engineered Bacteria To Modulate Amino Acid Metabolism Against Tumors

Bacterial-mediated synergistic cancer therapy(BMSCT)has been used as a promising tumor therapy approach.Living bacteria have attracted extensive research attention due to their good biocompatibility and active hypoxia targeting ability,as carriers to deliver genes and proteins into eukaryotic cells to treat various cancers.However,there are some disadvantages of bacterial therapy alone to be resolved,such as low tumor suppression rate and high biological toxicity in the treatment.In this study,we transcribed L-methionine-γ-lyase(Mde A)into Escherichia coli(E.coli)and loaded the approved photothermal agent indocyanine green(ICG),developed a novel light-controlled engineered bacterial E.coli-Mde A@ICG which synergistically regulates amino acid metabolism to fight tumors.Using the hypoxic tropism of E.coli,photothermal agents and Mde A were selectively delivered to the tumor region,and the bacteria replicated and expressed Mde A proteins.Under laser irradiation,photothermal lysed E.coli-Mde A to release the Mde A and consume the essential amino acid methionine(Met)in the tumor environment.In vitro cell experiments confirmed that the E.coli-Mde A+ NIR group could reach 90% of the 4T1 cells killing.In 4T1 tumor-bearing mouse models,E.coli-Mde A@ICG shows enhanced antitumor efficacy,along with 91.8% of the tumor growth inhibited.Apoptosis of tumor cells was 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.