纳米医学
放射治疗
癌症研究
背向效应
肿瘤微环境
犬尿氨酸
吲哚胺2,3-双加氧酶
重编程
免疫抑制
治疗指标
免疫系统
免疫原性细胞死亡
纳米颗粒
药理学
材料科学
医学
免疫疗法
化学
内科学
药品
纳米技术
免疫学
生物化学
肿瘤细胞
色氨酸
细胞
氨基酸
作者
Chunjie Wang,Ziliang Dong,Hao Yu,Yujie Zhu,Jing Ni,Quguang Li,Бо Лю,Yikai Han,Zhijuan Yang,Jianmei Wan,Kai Yang,Zhuang Liu,Liangzhu Feng
标识
DOI:10.1002/adma.202106520
摘要
Radiotherapy is widely exploited for the treatment of a large range of cancers in clinic, but its therapeutic effectiveness is seriously crippled by the tumor immunosuppression, mainly driven by the altered metabolism of cancer cells. Here, a pH-responsive nanomedicine is prepared by coating calcium carbonate (CaCO3 ) nanoparticles with 4-phenylimidazole (4PI), an inhibitor against indoleamine 2,3-dioxygenase 1 (IDO-1), together with zinc ions via the coordination reaction, aiming at reinforcing the treatment outcome of radiotherapy. The obtained pH-responsive nanomedicine, coined as acidity-IDO1-modulation nanoparticles (AIM NPs), is able to instantly neutralize protons, and release 4PI to suppress the IDO1-mediated production of kynurenine (Kyn) upon tumor accumulation. As a result, treatment with AIM NPs can remarkably enhance the therapeutic efficacy of radiotherapy against both murine CT26 and 4T1 tumors by eliciting potent antitumor immunity. Furthermore, it is shown that such combination treatment can effectively suppress the growth of untreated distant tumors via the abscopal effect, and result in immune memory responses to reject rechallenged tumors. This work highlights a novel strategy of simultaneous tumor acidity neutralization and IDO1 inhibition to potentiate radiotherapy, with great promises to suppress tumor metastasis and recurrence by eliciting robust antitumor immunity.
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