Chemically Enhanced Live Probiotic for In Vivo Tumor Targeting and Inhibition

Abstract

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.

Flame retarded polyurethane vitrimers containing isocyanurate rings: Synthesis and properties

“…According to the previous report, 18 the thermal stability of isocyanurate ring is much higher than that of carbamate. Therefore, in the first stage, the decomposition of urethane linkages and hydrocarbon chains takes place at 320°C, 53 while the degradation of the thermostable isocyanurate rings takes place in the second stage at 490°C 26 …”

Chemically engineering cells for precision medicine

“…For example, EcN was capable of transforming prodrug 5-fluorocytosine into 5-fluorouridine for tumor therapy, and chemical coating further improved their circulation and tumor colonization properties. 235 CAR-T cells have been genetically engineered to secrete enzymes, which can activate systemically injected prodrugs locally in tumor areas. 236 Chemical engineering tools can also be leveraged to incorporate the two components into one system to achieve a precisely controlled ''turn-on'' effect and better synergistic anti-tumor efficacy.…”

Driving Polymer Brushes from Synthesis to Functioning

“…Low toxic catalyst is also necessary, photo‐induced CRP like PET‐RAFT, [63] CRP with less toxic catalyst like SI‐ARGET ATRP, [115] were proven to prepare polymer brushes on the live cell surface controllably. Duan and co‐workers prepared PEG polymer brushes at the Escherichia coli Nissle 1917 (EcN) surface via PET‐RAFT to enhance the retention, tumor targeting, and colonization of probiotic EcN [116] …”

“…Duan and co-workers prepared PEG polymer brushes at the Escherichia coli Nissle 1917 (EcN) surface via PET-RAFT to enhance the retention, tumor targeting, and colonization of probiotic EcN. [116]…”