"Trojan Horse" Salmonella Enabling Tumor Homing of Silver Nanoparticles via Neutrophil Infiltration for Synergistic Tumor Therapy and Enhanced Biosafety.

selectively colonizes into the hypoxic tumor region and exerts antitumor effects via multiple mechanisms, while the tumor colonized recruits host neutrophils into the tumor, presenting a key immunological restraint to compromise the efficacy. Here, we develop a combinatorial strategy by employing silver nanoparticles (AgNPs) to improve the efficacy and biosafety of . 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 colonized tumor. The tumor-targeting AgNPs exert the functions of (1) local depletion of neutrophils in tumors to boost the efficacy of , (2) direct killing tumor cells via L-selectin-mediated intracellular delivery, and (3) clearing the residual 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.