放射敏感的纳米调节剂重新编程肿瘤-免疫细胞通讯用于免疫治疗  

Reprogramming tumor-immune cell communication with a radiosensitive nanoregulator for immunotherapy

作　　者：陈园园 刘淑杰 高鹏 潘伟 石明婉 王建波 李娜 唐波 Yuanyuan Chen;Shujie Liu;Peng Gao;Wei Pan;Mingwan Shi;Jianbo Wang;Na Li;Bo Tang(College of Chemistry,Chemical Engineering and Materials Science,Key Laboratory of Molecular and Nano Probes,Ministry of Education,Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong,Institute of Molecular and Nano Science,Shandong Normal University,Jinan 250014,China;Department of Radiation Oncology,Qilu Hospital,Cheeloo College of Medicine,Shandong University,Jinan 250012,China)

机构地区：[1]College of Chemistry,Chemical Engineering and Materials Science,Key Laboratory of Molecular and Nano Probes,Ministry of Education,Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong,Institute of Molecular and Nano Science,Shandong Normal University,Jinan 250014,China [2]Department of Radiation Oncology,Qilu Hospital,Cheeloo College of Medicine,Shandong University,Jinan 250012,China

出　　处：《Science China Materials》2023年第1期352-362,共11页中国科学（材料科学（英文版）

基　　金：supported by the National Natural Science Foundation of China(21927811 and 21874086);the Youth Innovation Science and Technology Program of Higher Education Institution of Shandong Province(2019KJC022)。

摘　　要：目前,将肿瘤相关巨噬细胞从促肿瘤生长的M2表型调节为抑制肿瘤生长的M1表型已成为一种有前途的肿瘤免疫治疗策略,但仍然具有挑战性,而且以可控的方式实现显得尤为困难.在此,我们报道了一种用于可时空激活免疫反应的放射敏感型纳米调节剂(AuDAP).AuDAP可通过多价相互作用同时识别和结合M2巨噬细胞与肿瘤细胞.在低剂量医用X射线照射下,纳米调节剂可介导产生大量活性氧(ROS),激活NF-κB信号通路,使M2型巨噬细胞复极化为M1型,从而原位激活巨噬细胞的免疫功能.一系列体外和体内实验结果表明,纳米调节剂可以有效重塑肿瘤细胞和巨噬细胞之间的通讯,并特异性地激活抗肿瘤免疫治疗.通过长时间观察发现,治疗组小鼠的原位肿瘤被明显抑制且未观察到肺部转移瘤的形成.该纳米调节剂可作为一种有潜力的纳米药物用于精确的肿瘤治疗,并能为可控的免疫治疗提供新的见解.Modulating tumor-associated macrophages from tumor-promoting M2 to tumoricidal M1 phenotype is promising for anti-tumor immunotherapy but remains challenging,especially in a controllable manner.Herein,we report a radiosensitive nanoregulator(Au DAP)for activatable immunotherapy.Au DAP can simultaneously recognize and bind M2 macrophages with tumor cells by polyvalent interactions.Under low-dose medical X-ray irradiation,the nanoregulator could generate reactive oxygen species(ROS)to activate the nuclear factor kappa-B(NF-κB)signaling pathway to repolarize M2 macrophages into M1 phenotype,thereby activating the immune function of macrophages in situ.A series of in vitro and in vivo experiments demonstrated the cell communication remodeling and immunotherapy activation effects of Au DAP.As a result,Au DAP+X-ray inhibited the growth of tumors and effectively prevented their metastasis during a long period of observation.This nanoregulator may serve as a promising nanomedicine for precise tumor therapy,and this work offers new insights for activatable immunotherapy.

关 键 词：肿瘤免疫治疗 M2型巨噬细胞 肿瘤相关巨噬细胞 复极化 免疫细胞 肿瘤治疗 纳米药物 体内实验 

分 类 号：R730.51[医药卫生—肿瘤]