School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China.
Guangdong Provincial Key Laboratory of Fermentation and Enzyme Engineering, South China University of Technology, Guangzhou 510006, China.
Int J Mol Sci. 2023 Jul 7;24(13):11222. doi: 10.3390/ijms241311222.
Tumor-associated macrophages (TAMs) promote tumor development and metastasis and are categorized into M1-like macrophages, suppressing tumor cells, and M2-like macrophages. M2-like macrophages, occupying a major role in TAMs, can be repolarized into anti-tumoral phenotypes. In this study, outer membrane vesicles (OMVs) secreted by Nissle 1917 carry perhexiline (OMV@Perhx) to explore the influence of OMVs and perhexiline on TAM repolarization. OMV@Perhx was internalized by macrophages and regulated the phenotype of TAMs from M2-like to M1-like efficiently to increase the level of tumor suppressor accordingly. Re-polarized macrophages promoted apoptosis and inhibited the mobility of tumor, cells including invasion and migration. The results indicate that OMVs improve the efficacy of perhexiline and also represent a promising natural immunomodulator. Combining OMVs with perhexiline treatments shows powerfully synergistic anti-tumor effects through co-culturing with re-polarized macrophages. This work is promising to exploit the extensive applications of OMVs and chemical drugs, therefore developing a meaningful drug carrier and immunomodulator as well as expanding the purposes of traditional chemical drugs.
肿瘤相关巨噬细胞（TAMs）促进肿瘤的发展和转移，并可分为抑制肿瘤细胞的 M1 样巨噬细胞和 M2 样巨噬细胞。在 TAMs 中占主要地位的 M2 样巨噬细胞可以被重新极化为抗肿瘤表型。在这项研究中，Nissle 1917 分泌的外膜囊泡（OMVs）携带己酮可可碱（OMV@Perhx），以探讨 OMVs 和己酮可可碱对 TAM 重极化的影响。OMV@Perhx 被巨噬细胞内化，并有效地将 TAMs 的表型从 M2 样调节为 M1 样，从而相应地增加肿瘤抑制因子的水平。重极化的巨噬细胞促进了肿瘤细胞的凋亡并抑制了其迁移和侵袭等运动能力。结果表明，OMVs 提高了己酮可可碱的疗效，同时也代表了一种很有前途的天然免疫调节剂。通过与重极化的巨噬细胞共培养，OMVs 与己酮可可碱联合治疗显示出强大的协同抗肿瘤作用。这项工作有望开发出广泛应用的 OMVs 和化学药物，从而为传统化学药物的载体和免疫调节剂的开发以及用途拓展提供了新的思路。
