北京理工大学生命学院,北京 100081
国家杰出青年科学基金(22025401) 和国家自然科学基金 (22293034,22293030,32101140) 资助项目。
School of Life Science, Beijing Institute of Technology, Beijing 100081, China
This work was supported by grants from the National Science Fund for Distinguished Young Scholars (22025401) and The National Natural Science Foundation of China (22293034, 22293030, 32101140).
细菌外膜囊泡(outer membrane vesicles,OMVs)是由革兰氏阴性菌分泌的纳米囊泡,主要由细菌外膜和周质成分组成,因此表面富集的病原体相关分子模式(PAMPs)使OMVs能激起强烈的免疫反应。在抗肿瘤研究中,OMVs主要被用于抗肿瘤药物的递送,不仅能增加药物的肿瘤富集还能激活免疫反应协同杀伤肿瘤;同时,OMVs也用于开发肿瘤疫苗的佐剂,可显著提高免疫响应的能力。本综述主要概括了OMVs的生物发生机理、OMVs对宿主免疫系统的影响及其在肿瘤治疗中的研究进展。
Outer membrane vesicles (OMVs) are nanoscale vesicles secreted by Gram-negative bacteria. As a unique bacterial secretion, OMV secretion can help bacteria maintain the outer membrane stability or remove harmful substances. Studies have shown that local separation of outer membrane and peptidoglycan layers led by abnormalities in outer membrane protein function, abnormal structure or excessive accumulation of LPS, and erroneous accumulation of phospholipids in the outer leaflet, which can all lead to bacterial outer membrane protrusion and eventually bud formation of OMVs. Since OMVs are mainly composed of bacterial outer membrane and periplasmic components, the pathogen associated molecular patterns (PAMPs) on their surface can trigger strong immune responses. For example, OMVs can recruit and activate neutrophils, polarize macrophages to secrete large amounts of inflammatory factors. More importantly, OMVs can act as adjuvants to induce dendritic cell (DC) maturation to enhance adaptive immune response in the body. At the same time, OMVs are derived from bacteria, which make it easy to modify. The methods by genetic engineering and others can improve their tumor targeting, give them new functions, or reduce their immunotoxicity, which is conducive to their application in tumor therapy. OMVs not only induce apoptosis or pyroptosis of tumor cells, but also regulate the host immune system, which makes OMVs themselves have a certain killing effect on tumors. In addition, the tendency of neutrophils to inflammatory tumor sites and the formation of neutrophil extracellular traps enable OMVs to target tumor sites, and the suitable size and the characteristic that they are easily taken up by DCs give OMVs a certain lymphatic targeting ability. Therefore, OMVs are often employed as excellent drug or vaccine carriers in tumor therapy. This review mainly discusses the biological mechanism of OMVs, the regulatory effects of OMVs on immune cells, the functional modification strategies of OMVs, and their research progress in tumor therapy.
王云锋,庄婉茹,马宪彬,聂伟东,谢海燕.细菌外膜囊泡应用于肿瘤治疗[J].生物化学与生物物理进展,2024,51(2):309-327
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