A Customized Biohybrid Presenting Cascade Responses to Tumor Microenvironment

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Microbiology

Background:

• Microorganisms face limitations in medical use due to metabolism, byproducts, and proliferation.
• Targeted tumor therapy requires precise mechanisms for cancer cell destruction.

Purpose of the Study:

• To engineer a biohybrid system for efficient cancer site targeting and precise tumor ablation.
• To utilize a pre-determined metabolic pathway for enhanced therapeutic outcomes.

Main Methods:

• Engineered DH5α Escherichia coli with hypoxia-inducible promoters and lactate oxidase genes.
• Surface-armored bacteria with iron-doped ZIF-8 nanoparticles.
• Utilized nanoparticles' peroxidase-like activity to generate cytotoxic hydroxyl radicals.

Main Results:

• Engineered E. coli produced lactate oxidase in hypoxic tumor environments, reducing lactate.
• Nanoparticles converted hydrogen peroxide into hydroxyl radicals, inducing ferroptosis.
• The biohybrid significantly inhibited tumor growth and metastasis following intravenous injection.

Conclusions:

• The developed biohybrid offers a novel strategy for targeted tumor therapy.
• This approach overcomes limitations of traditional microorganism-based therapies.
• The engineered system demonstrates potent anti-tumor efficacy and potential for clinical translation.