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

作者：Ze Mi, Lina Guo, Peng Liu, Yan Qi, Zhichao Feng, Jiahao Liu, Zhenhu He, Xiao Yang, Shengnan Jiang, Jianzhen Wu, Jinsong Ding, Wenhu Zhou, Pengfei Rong · 发表于：Nano Letters · 年份：2020 · DOI：10.1021/acs.nanolett.0c03811 · 被引用次数：82 · 研究领域：Cancer Research and Treatments、Nanoplatforms for cancer theranostics、Graphene and Nanomaterials Applications

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.