Salmonella selectively colonizes into the hypoxic tumor region and exerts antitumor effects via multiple mechanisms, while the tumor colonized Salmonella recruits host neutrophils into the tumor, presenting a key immunological restraint to compromise the Salmonella efficacy. Here, we develop a combinatorial strategy by employing silver nanoparticles (AgNPs) to improve the efficacy and biosafety of Salmonella. The AgNPs were decorated with sialic acid (SA) to allow selective recognition of L-selectin on neutrophil surfaces, based on which the tumor-homing of AgNPs was achieved by neutrophil infiltration in the Salmonella colonized tumor. The tumor-targeting AgNPs exert the functions of (1) local depletion of neutrophils in tumors to boost the efficacy of Salmonella, (2) direct killing tumor cells via L-selectin-mediated intracellular delivery, and (3) clearing the residual Salmonella after complete tumor eradication to minimize the side effects. With a single tail vein injection of such combination treatment, the tumor was eliminated with high biosafety, resulting in a superior therapeutic outcome.
Keywords: bacteria-mediated cancer therapy; combination therapy; hypoxia; immunity; melanoma; targeting.