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.

Nanomaterial‐assisted oncolytic bacteria in solid tumor diagnosis and therapeutics

“…Researchers modified E. coli to express the l‐methionine‐ γ ‐cleaving enzyme (MdeA) and loaded it with indocyanine green (ICG). In response to near‐infrared laser irradiation, the complex released MdeA and depleted the essential amino acid methionine (Met) to disrupt the balance of the TME 27 . Eubacterium hallii deposited by iron‐polyphenol nanoparticles sustained the conversion of intratumoral lactate to butyrate, inhibiting the polarization of pro‐tumor M2‐like macrophages 110…”

“…As therapeutic agents, multifunctional nanomaterials bestow oncolytic bacteria with characteristics that surpass their inherent capabilities. The physicochemical properties of nanomaterials allow oncolytic bacterial therapy to synergize therapeutic effects with photothermal therapy (PTT), photodynamic therapy (PDT), chemotherapy, radiotherapy, immunotherapy, and other modalities 27–31 . These nanomaterials also serve as imaging probes, generating specific signals for tumor therapy visualization 32 .…”

“…The physicochemical properties of nanomaterials allow oncolytic bacterial therapy to synergize therapeutic effects with photothermal therapy (PTT), photodynamic therapy (PDT), chemotherapy, radiotherapy, immunotherapy, and other modalities. 27 , 28 , 29 , 30 , 31 These nanomaterials also serve as imaging probes, generating specific signals for tumor therapy visualization. 32 Nanomaterial‐assisted oncolytic bacteria (NAOB) further broaden the means and modes of oncolytic bacterial therapy, leading to precision tumor therapy.…”

Achieving deep intratumoral penetration and multimodal combined therapy for tumor through algal photosynthesis

“…For example, engineered bacteria modified with Fe 3 O 4 nanoparticles have been utilized for tumor immunotherapy under magnetic field control [ 17 ]. Gene-engineered bacteria for photothermal lysis have been employed to regulate amino acid metabolism, thereby inhibiting tumor growth [ 18 ]. Additionally, utilizing photosynthetic activity of algae to generate oxygen helps alleviate the local tumor hypoxic microenvironment, enhancing the efficacy of photodynamic therapy [ 19 ].…”