Hypoxia-responsive soft biohybrid bacteria for breast cancer therapy

Because of their distinct physical and chemical characteristics, soft materials with low modulus, great deformability, and large compliance have progressively emerged as a significant area of study. However, the responsiveness of traditional soft materials is inherently limited by passive diffusion and equilibrium thermodynamics. Thus, by incorporating stimuli-responsive artificial materials into motile bacterial species with anticancer properties, a soft biohybrid bacterial system has been created, converting soft materials from static scaffolding into adaptable, living systems. Specifically, the surface of Escherichia coli DH5α is modified by liposomes co-loaded with glucose oxidase and Tirapazamine (TPZ). The soft biohybrid bacterial system uses anaerobic targeting to deliver anticancer drugs and catalyzes glucose in the tumor microenvironment, consuming local oxygen in the process. The enhanced hypoxic microenvironment fully activates TPZ, significantly boosting its cytotoxic effect on tumor cells. Moreover, the soft biohybrid bacterial system further induces strong immunogenic cell death, which enhances the therapeutic effect while minimizing side effects on normal tissues. This innovative strategy offers a promising solution to overcome the therapeutic challenges associated with traditional soft materials.