期刊
ACS APPLIED MATERIALS & INTERFACES
卷 13, 期 17, 页码 19825-19835出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.1c04638
关键词
iron oxide; nanoparticles; tumor microenvironment; reprograming; macrophage
资金
- National Natural Science Foundation of China [22077119]
- Science and Technology Development Project Foundation of Jilin Province [20200404129YY]
- Budgeted Capital Construction Foundation of Jilin Province [2020C035-4]
- Guangdong Basic and Applied Basic Research Foundation for Distinguished Young Scholars [2020B1515020027]
- Guangzhou Science and Technology Bureau [202002020070, 201902020015]
- Guangdong Science and Technology Department [2020B1212060018, 2020B1212030004]
The study utilized hollow Fe3O4 nanoparticles to reprogram TAMs towards M1 phenotype, activating antitumor immune responses and releasing nitric oxide for synergistic therapy against cancer.
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-alpha, and producing high levels of NO, leading to synergistic tumor therapy.
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