Reassembly nanomaterials-mediated engineered bacteria lysis for reshaping immunosuppressive microenvironment.

Area of Science:

• Biomedical Engineering
• Cancer Therapy
• Immunology

Background:

• Bacterial therapy shows promise for cold tumors but faces challenges like microenvironment interference and tumor-promoting metabolites.
• Genetically modified bacteria can deliver immune activators, but control and safety remain concerns.

Purpose of the Study:

• To develop a bacteria-nanomaterial hybrid system (IE-PPCs) for stable, controllable immune factor delivery and enhanced cancer treatment safety.
• To engineer E. coli Nissle 1917 (EcN) to express IFN-γ and anchor it onto a nanomaterial carrier.

Main Methods:

• Engineered EcN expressing IFN-γ, anchored onto peptide-functionalized nanomaterials (PPCs).
• Controlled IFN-γ expression via IPTG induction.
• Demonstrated IE-PPCs tumor homing, MMP-triggered nanostructure transformation, bacterial lysis, and immune factor release in 4T1 mouse models.

Main Results:

• IE-PPCs selectively colonized tumors, releasing IFN-γ and bacterial lysates upon MMP-triggered lysis.
• IFN-γ inhibited tumor proliferation; combined therapy promoted dendritic cell maturation and M1 macrophage polarization.
• IE-PPCs plus anti-PD-L1 achieved an 89.7% anti-tumor rate with a 98.9% reduction in tumor bacterial load.

Conclusions:

• The IE-PPCs system offers a breakthrough strategy for reshaping immunosuppressive tumor microenvironments.
• This approach provides a safe and effective therapeutic option for cancer treatment by combining bacterial therapy and nanomaterials.