Chemically Enhanced Live Probiotic for In Vivo Tumor Targeting and Inhibition

Live probiotic-mediated therapy suffers from the contradiction between treatment efficiency and bacterial pathogenicity that is the major barrier for clinical applications. Herein, we reported a chemically enhanced strategy to promote the tumor colonization ability of probiotic Escherichia coli Nissle 1917 (EcN) by prolonging the blood reservation with a lower inflammatory reaction. The chain-transfer agent (CTA) reacted with the amino groups on the EcN surface, and PEG polymer brushes from CTA were synthesized to produce the polymer-coated bacteria (PCB). PCB has negligible differences in the morphology and viability with EcN but possesses significantly enhanced blood reservation and tumor colonization ability. The lower level of secreted cytokines and white blood cells indicated a reduced inflammatory reaction, which promoted tumor colonization. More importantly, PCB can convert prodrug 5-fluorocytosine (5-FC) into 5-fluorouridine (5-FU) for tumor treatment. The PCB + 5-FC treatment inhibited tumor growth as high as 56.1 ± 11.1%, which is significantly higher than the EcN + 5-FC treatment (19.0 ± 9.9%). This strategy promoted the safety and the efficacy of bacteria in live bacterial-mediated antitumor therapy and showed great potential for clinical applications.