A research team led by Professor Wu Yuzhou from the School of Chemistry and Chemical Engineering at Huazhong University of Science and Technology (HUST) has developed a neutrophil-inspired programmable bacteria (NPB) system, offering a novel programmable modular platform for precision cancer immunotherapy. The study, titled "Neutrophil-Inspired Programmable Bacteria for Pyroptosis-Driven Tumor Eradication", was published in the Journal of the American Chemical Society.

Neutrophils can reside at pathological sites and eliminate abnormal cells. However, their functionality is often altered in the tumor microenvironment, making them unsuitable as direct therapeutic tools. To address this challenge, the team used the nonpathogenic Escherichia coli MG1655 strain as a chassis to develop a synthetic biology-based sequential treatment system, which replicates the "homing – bursting – lethality" mechanism of neutrophils, targeting cancer precisely.

The platform incorporates a four-stage cascade control: the engineered bacteria preferentially colonize hypoxic tumor regions; under focused ultrasound and facilitated by Vitreoscilla hemoglobin, they generate reactive oxygen species, enabling bacterial lysis and controlled therapeutic protein release; gelatinase present in tumor tissues activates granzyme B zymogen; pyroptosis enhances systemic antitumor immunity.

In murine models of CT26 colorectal cancer, the NPB system combined with focused ultrasound effectively inhibited primary tumor growth, significantly reduced lung metastases, with increased CD8⁺ T-cell infiltration and decreased FoxP3⁺ regulatory T cells in tumor tissues.

Integrating physical ultrasound activation with tumor-specific biochemical triggers, this platform represents a paradigm shift in the spatiotemporal programming of engineered bacteria, offering innovative solutions for precision cancer therapies.

HUST is the primary corresponding institution for the study, with PhD student Zhang Junshuai as the first author and Professor Wu Yuzhou as the corresponding author.

Source: School of Chemistry and Chemical Engineering, HUST