Probiotic-inspired hybrid nanovesicles for enhancing immune checkpoint therapy efficiency via tumor immune microenvironment modulation

作者：Fang Wang, Jinghao Fan, Wenping Pan, Mingkang Liu, Jiaxin Wang, Xue Wei, Yiwen Xian, Shiyi Chen, Chunhong Cui, Yongmiao Chen, Kai Li, Ling Guo, Yezi You, Hongmei Liu, Decheng Wu · 发表于：Bioactive Materials · 年份：2025 · DOI：10.1016/j.bioactmat.2025.10.012 · 被引用次数：5 · 研究领域：Nanoplatforms for cancer theranostics、Extracellular vesicles in disease、Cancer Immunotherapy and Biomarkers

Immunologically “cold” tumors, characterized by low immune cells infiltration, represent a significant obstacle to the success of immune checkpoint therapy. Intestinal microbiome therapy has emerged as a potential strategy to overcome this challenge by reprogramming the immune microenvironment. However, its clinical application is constrained by unresolved safety concerns. To address these challenges, we fused Escherichia coli -secreted outer membrane vesicle (OMV) with the macrophage membrane vector (RV) to construct hybrid nanovesicle (ROMV) and encapsulated the bacterial metabolite trimethylamine N -oxide (TMAO), forming ROMV/TMAO. ROMV/TMAO mimicked the beneficial functions of intestinal probiotics by leveraging the immunomodulatory properties of OMV and TMAO, combined with the tumor-homing capabilities of RV. In human lung cancer organoids and multiple tumor models, selective tumor targeting and accumulation of ROMV/TMAO facilitated M1 polarization of tumor-associated macrophages and enhanced CD8 + T lymphocyte infiltration, ultimately inhibiting tumor growth. When combined with ROMV/TMAO, the immune checkpoint inhibitor α-PD-L1 exhibited superior antitumor efficacy than monotherapy. This study introduces a probiotic-inspired nanotherapeutic strategy for augmenting immune checkpoint therapy outcomes while addressing microbiome therapy safety challenges. probiotic-inspired nanomaterials for augmenting immune checkpoint therapy (ICT) outcomes while addressing microbiome th...