免疫疗法
癌症研究
癌症免疫疗法
癌症
腺苷
免疫系统
医学
化学
免疫学
内科学
作者
Ningyue Yu,Meng Li,Yijing Zhang,Fengshuo Wang,Xiangrong Yu,Rong Cai,Jingchao Li
出处
期刊:Nano Today
[Elsevier]
日期:2023-10-01
卷期号:52: 101944-101944
被引量:5
标识
DOI:10.1016/j.nantod.2023.101944
摘要
Although the combinations of immunotherapy with other therapies can offer promising possibility to sensitize tumors to various immunotherapeutic strategies for amplified antitumor immune responses, the up-regulations of immunosuppressive pathways after cancer treatments still greatly compromise the therapeutic outcomes. Herein, we report the dual-modulation of up-regulated immunosuppressive pathways by designing sono-activatable semiconducting polymer nanofeedbacks (SPNSA) for cancer immunotherapy. The SPNSA are constructed to contain semiconducting polymer nanoparticles (SPNs) as the sonosensitizers, adenosine receptor A2A antagonist (SCH58261), programmed death-ligand 1 (PD-L1) antibody (aPD-L1) and singlet oxygen (1O2)-cleavable linkers. Upon ultrasound (US) irradiation, the SPNs produce 1O2 for sonodynamic therapy (SDT) and inducing immunogenic cell death (ICD) with up-regulations of adenosine level and PD-L1 expression. In addition, the produced 1O2 can snip the 1O2-cleavable linkers for on-demand release of SCH58261 and aPD-L1 that act as the feedbacks to modulate the up-regulated immunosuppressive adenosine and PD-L1 pathways simultaneously, resulting in further amplified antitumor immunological effect. In the bilateral tumor-bearing mouse models, the administration of SPNSA and sono-activation can greatly inhibit the tumor growths and metastasis. This study thus provides a sono-activatable nanoplatform for precisely amplifying immunotherapeutic effect via feedback modulating of immunosuppressive pathways post-treatments.
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