Active tumor-therapeutic liposomal bacteriobot combining a drug (paclitaxel)-encapsulated liposome with targeting bacteria (Salmonella Typhimurium)

• Active tumor targeting bacteriobots were fabricated combining bacteria and liposomes.
• Biotin–streptavidin affinity was used as a binding mechanism.
• Salmonella Typhimurium could enhance motility of drug-loaded liposomes.
• Bacteria could drive drug-loaded liposomes to tumor cells.
• Bacteriobots showed better therapeutic effect than drug-loaded liposomes.

We propose a new tumor-therapeutic bacteria-based microrobot (bacteriobot) combining a paclitaxel-loaded liposomal microcargo with tumor-targeting Salmonella Typhimurium bacteria. The tumor-therapeutic liposomal bacteriobot was constructed by binding biotin molecules displayed on the outer membrane proteins of the bacteria and streptavidin coated on the drug-loaded liposomes. First, we performed a motility analysis of the bacteriobot, where the bacteria-actuated liposomes showed much higher average velocity (3.09 ± 0.44 μm/s) than the liposomes without bacterial actuation (0.40 ± 0.14 μm/s). Second, we performed a cytotoxicity test using a breast cancer cell line (4T1) to check the tumor-therapeutic efficacy of the bacteriobots. The drug-loaded bacteriobots (IC50 = 16.48 ± 0.43 μg/ml) showed better tumor-killing ability than the drug-containing liposomes (IC50 = 21.91 ± 0.74 μg/ml). Moreover, the bacteriobots showed strong tumor-targeting and killing properties in a simple co-culture chamber containing normal cells (NIH/3T3) and cancer cells (4T1). These results revealed that the constructed bacteriobots can be used for active tumor therapy.