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人工自然杀伤细胞特异性抑制肿瘤和重新教育叛变巨噬细胞。

Artificial Natural Killer Cells for Specific Tumor Inhibition and Renegade Macrophage Re-Education.

机构信息

The Institute for Advanced Studies, Wuhan University, Wuhan, 430072, P. R. China.

Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan, 430072, P. R. China.

出版信息

Adv Mater. 2019 Oct;31(43):e1904495. doi: 10.1002/adma.201904495. Epub 2019 Sep 9.

Abstract

Natural killer (NK) cells can not only recognize and eliminate abnormal cells but also recruit and re-educate immune cells to protect the host. However, the functions of NK cells are often limited in the immunosuppressive tumor microenvironment (TME). Here, artificial NK cells (designated as aNK) with minor limitations of TME for specific tumor killing and renegade macrophage re-education are created. The red blood cell membrane (RBCM) cloaks perfluorohexane (PFC) and glucose oxidase (GOX) to construct the aNK. The aNK can directly kill tumor cells by exhausting glucose and generating hydrogen peroxide (H O ). The generated H O is also similar to cytokines and chemokines for recruiting immune cells and re-educating survived macrophages to attack tumor cells. In addition, the oxygen-carried PFC can strengthen the catalytic reaction of GOX and normalize the hypoxic TME. In vitro and in vivo experiments display that aNK with slight TME limitations exhibit efficient tumor inhibition and immune activation. The aNK will provide a new sight to treat tumor as the supplement of aggressive NK cells.

摘要

自然杀伤 (NK) 细胞不仅可以识别和消除异常细胞,还可以招募和重新教育免疫细胞来保护宿主。然而,NK 细胞的功能在免疫抑制性肿瘤微环境 (TME) 中往往受到限制。在这里,我们创建了具有 TME 轻微限制的人工 NK 细胞(命名为 aNK),用于特异性杀伤肿瘤和重新教育叛变的巨噬细胞。红细胞膜 (RBCM) 包裹全氟己烷 (PFC) 和葡萄糖氧化酶 (GOX) 以构建 aNK。aNK 可以通过耗尽葡萄糖和生成过氧化氢 (H2O2) 直接杀死肿瘤细胞。生成的 H2O2 也类似于细胞因子和趋化因子,用于招募免疫细胞并重新教育存活的巨噬细胞以攻击肿瘤细胞。此外,载氧的 PFC 可以增强 GOX 的催化反应并使缺氧 TME 正常化。体外和体内实验显示,具有轻微 TME 限制的 aNK 表现出高效的肿瘤抑制和免疫激活。作为激进 NK 细胞的补充,aNK 将为治疗肿瘤提供新的思路。

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