Biomaterials | Recombinant Nanomaterial-Mediated Engineering Bacterial Lysis Technology for Reshaping Immunosuppressive Microenvironment

Bacterial therapy is a promising strategy aimed at reshaping the immunosuppressive microenvironment of "cold" tumors, thanks to the inherent tumor-targeting and immune-regulating capabilities of bacteria. Bacteria can precisely and continuously release immune activators at the tumor site through synchronous lysis circuits or external physical triggers (such as photothermal and magneto-thermal methods). However, the tumor microenvironment (hypoxia and acidity) interferes with the efficiency of gene expression, while bacterial metabolites (butyric acid and lactic acid) may pose a risk of promoting tumors. This study developed a bacterial-nanomaterial hybrid system (IE-PPCs) to achieve stable and controllable delivery of immune factors and enhance treatment safety. The IFN-γ gene was transformed into Escherichia coli Nissle 1917 (EcN) and anchored to PPCs composed of antimicrobial peptides, MMP-cleavable peptides, and hydrophilic PEG. The expression of IFN-γ in IE-PPCs was precisely regulated by IPTG before administration. After intravenous injection, IE-PPCs selectively colonize in the tumor microenvironment, and then MMP-responsive PPCs spontaneously transform into fibrous nanostructures, exposing antimicrobial peptide residues, thereby lysing bacteria and releasing IFN-γ and bacterial lysates. IFN-γ directly inhibits tumor proliferation, and when combined with bacterial lysate, it can induce the maturation of dendritic cells and promote M1 macrophage polarization. In the 4T1 mouse breast cancer model, IE-PPC combined with anti-PD-L1 therapy achieved a 89.7% tumor anti-cancer rate, and the bacterial load within the tumor decreased by 98.9%. The IE-PPCs system provides a breakthrough strategy for reshaping the immunosuppressive microenvironment and offers a reliable and attractive treatment option for cancer patients.
This study was published in Biomaterials under the title "Reassembly nanomaterials-mediated engineered bacterial lysis for reshaping immunosuppressive microenvironment".
References:
DOI: 10.1016/j.biomaterials.2026.124148