Bacteria-propelled microrockets to promote the tumor accumulation and intracellular drug uptake

[Display omitted] •Microrocket is constructed by assembly of one bacterium as the bioengine into a microtube.•Microtubes are fabricated by layer-by-layer assembly of alginate and chitosan in porous template.•Bacteria drive the rocket-like directional motion of microtubes in both water and viscous media.•Microrockets enhance the blood-tumor tissue extravasation and internalization into tumor cells.•Demonstrate a novel strategy to combat multiple biological barriers in the drug delivery pathway. To address the biological or pathological barriers, the self-propulsion abilities of drug carriers may bring distinct improvements when compared to passive diffusion. In the current study bacteria-propelled microtubular rockets are proposed to enhance the extravasation from blood circulation, penetration in the tumor matrix and intracellular drug uptake. Microtubes with loaded doxorubicin (MTDOX) are constructed via layer-by-layer deposition of oxidized alginate (O-Alg) and chitosan in sacrificial porous membranes, followed by crosslinking via schiff’s base bonds to regulate drug release. Under a concentration gradient of L-aspartate as the chemoattractant, E. coli Nissle1917 (EcN) are embedded into microtubes as bioengines to obtain MTDOX@EcN microrockets. The assembled EcN provide aligned propulsion forces and directional trajectories like a microrocket, exhibiting high motion velocities in both water and viscous media. The uptake efficiency of MTDOX@EcN by tumor cells shows over 2.1 folds higher than that of MTDOX, indicating that the EcN propulsion could promote the cell internalization of MTDOX. After intravenous injection of MTDOX@EcN, the DOX levels in tumors reach 6.1 folds higher than those of MTDOX after 7 days, suggesting that the EcN-propelled rocket-like motion could promote the extravasation from blood circulation and the retention in tumors. Compared with other treatment, MTDOX@EcN could significantly inhibit the tumor growth, increase the survival rate of animals, and avoid side effects like hematologic, hepatic and renal toxicities. Herein, the bacteria-propelled microrockets demonstrate a feasible strategy to boost therapeutic efficacy of anticancer agents by combating multiple biological barriers in the drug delivery pathway.