Microbiotic nanomedicine for tumor-specific chemotherapy-synergized innate/adaptive antitumor immunity

Recently, microbiotic nanomedicine has shown great promise in the field of tumor therapy. In this work, we report a novel microbiotic nanomedicine denoted as LOD/TPZ@Lips-LA, which was constructed by anchoring lactate oxidase (LOD)-and prodrug tirapazamine (TPZ)-coloaded liposomes on the surface of lactobacillus (LA) through amide condensation reaction for chemotherapy-synergized antitumor immunity. TPZ and LOD were efficiently delivered to neoplastic tissue by the tumor-targeting nature of LA, wherein the nanomedicine induced significant tumor cell apoptosis by in situ ROS generation and TPZ activation based on the metabolism of LA, thus evoking robust immunogenic cell death (ICD). More importantly, LOD/TPZ@ Lips-LA-induced ICD induces strong anticancer immunity featuring anti-tumorigenic M1 polarization of innate tumor-associated macrophages and infiltration of adaptive cytotoxic CD8+ T cells in tumors by the marked biomarker expression regulations, thereby synergetically amplifying the tumor inhibition effects of the designed microbiotic medicine. Such a strategy of LOD/TPZ@Lips-LA enabled ICD based on bacterial metabolism and synergized antitumor immunity provides a promising paradigm for highly effective cancer therapeutics by designing novel microbiotic nanomedicine in the future.(c) 2022 Elsevier Ltd. All rights reserved.

Automated summary

This study reports a novel microbiotic nanomedicine LOD/TPZ@Lips-LA, which combines lactate oxidase (LOD) and prodrug tirapazamine (TPZ) loaded liposomes anchored on lactobacillus (LA) surface for chemotherapy-synergized antitumor immunity. The nanomedicine induces tumor cell apoptosis through in situ ROS generation and TPZ activation based on LA metabolism, resulting in strong immunogenic cell death (ICD). By regulating biomarker expression, it promotes anti-tumorigenic M1 polarization of innate tumor-associated macrophages and infiltration of adaptive cytotoxic CD8+ T cells, synergistically enhancing the tumor inhibition effects.