Polydopamine-Modified Engineered E. coli for Synergistic Cancer Therapy via Glucose Oxidase-Mediated Starvation and Prodrug Delivery

Abstract: this study aims to gather dopamine (PDA) modified engineering bacteria load glucose oxidase (bigger) and former drug taxol, and realize the tumor targeting hungry treatment and the synergy of taxol drug delivery. By taking advantage of the specific tumor-targeting characteristics of Escherichia coli as a carrier, the recognition and endocytosis ability of tumor cells are enhanced through the camouflage properties of its cell membrane. GOx catalyzes the oxidation of glucose within tumor cells to produce hydrogen peroxide (HO₂), thereby inducing a "starvation" state in tumor cells and inhibiting their proliferation and metabolism. Meanwhile, paclitaxel prodrugs are reduced to active paclitaxel in the tumor microenvironment (TME), exerting anti-tumor effects. This system achieves the synergistic treatment of tumors through a dual mechanism.

The results indicate that PDA-modified E. coli co-loaded with GOx and a paclitaxel prodrug exhibits considerable inhibitory effects against various tumor cell lines in vitro, as well as effective tumor suppression in vivo. Compared with the administration of either GOx or paclitaxel alone, this integrated therapeutic system achieves enhanced treatment outcomes in terms of both tumor growth inhibition and survival extension. Moreover, the system demonstrates favorable site-specific drug release behavior, which effectively mitigates tumor hypoxia and consequently improves overall therapeutic performance.