光动力疗法
免疫系统
癌症研究
免疫疗法
体内
肿瘤微环境
肿瘤缺氧
免疫检查点
联合疗法
缺氧(环境)
医学
化学
药理学
免疫学
放射治疗
生物
内科学
氧气
有机化学
生物技术
作者
Yanlei Liu,Yun‐Xiang Pan,Wenwu Cao,Fangfang Xia,Bin Liu,Jiaqi Niu,Gabriel Alfranca,Xuejian Sun,Lijun Ma,Jesús M. de la Fuente,Jie Song,Jian Ni,Daxiang Cui
出处
期刊:Theranostics
[Ivyspring International Publisher]
日期:2019-01-01
卷期号:9 (23): 6867-6884
被引量:118
摘要
The low efficiency of photodynamic therapy (PDT) is caused by tumor hypoxia and the adaptive immune resistance/evasion of tumor cells, while the currently emerging immune checkpoint therapy restores the intrinsic immune capacities but can't directly attack the tumor cells. Methods: Herein we report an integrated nanoplatform that combines PDT with immunotherapy to enhance photodynamic therapeutic effects and simultaneously inhibit tumor cells resistance/evasion. To achieve this, we fabricated Mn@CaCO3/ICG nanoparticles and loaded them with PD-L1-targeting siRNA. Results: Thanks to the protection of CaCO3 on the loaded ICG and the oxygen produced by MnO2, an enhanced photodynamic therapeutic effect in vitro was observed. In vivo experiments demonstrated that the nanoplatform could efficiently deliver the loaded drug to the tumor tissues and significantly improve tumor hypoxia, which further contributes to the therapeutic effect of PDT in vivo. Moreover, the synergistic benefits derived from the siRNA, which silenced the checkpoint gene PD-L1 that mediates the immune resistance/evasion, resulted in a surprising therapeutic effect to rouse the immune system. Conclusions: The combination treatment strategy has great potential to be developed as a new and robust method for enhanced PDT therapy with high efficiency and a powerful antitumor immune response based on PD-L1 blockade.
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