肿瘤微环境
一氧化氮
促炎细胞因子
癌症研究
免疫疗法
材料科学
免疫监视
癌症免疫疗法
免疫系统
巨噬细胞
体外
体内
化学
免疫学
炎症
生物
生物化学
有机化学
生物技术
作者
Xiaqing Wu,Yan Cheng,Rong Zheng,Keqiang Xu,Jiao Yan,Panpan Song,Yanjing Wang,Abdur Rauf,Yue Pan,Haiyuan Zhang
标识
DOI:10.1021/acsami.1c04638
摘要
Tumor-associated macrophages (TAMs) of M2 phenotype have mediated the immunosuppression in a tumor microenvironment, facilitating the escape of tumor cells from immunosurveillance. Reprograming the immunosuppressive M2 TAMs to immunostimulatory M1 phenotype can activate the antitumor immune responses for cancer immunotherapy. Herein, hollow iron oxide (Fe3O4) nanoparticles (NPs) were employed to reprogram M2 TAMs toward M1 TAMs, aiming to release proinflammatory cytokines and recruit T cells to kill tumor cells. After loaded with l-arginine (l-Arg) and sealed with poly(acrylic acid) (PAA), hollow Fe3O4 NPs were fabricated into LPFe3O4 NPs, which could release l-Arg based on pH-responsive PAA and produce nitric oxide (NO) with the help of nitric oxide synthase (iNOS) overexpressed by M1 TAMs, as a result of additional tumor elimination for gas therapy. In vitro and in vivo studies demonstrate that LPFe3O4 NPs could effectively reprogram M2 to M1 macrophages, activating T cells, releasing TNF-α, and producing high levels of NO, leading to synergistic tumor therapy.
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