光动力疗法
CTL公司*
肿瘤微环境
单线态氧
免疫疗法
细胞毒性T细胞
癌症
医学
纳米医学
连接器
癌症研究
癌症免疫疗法
免疫系统
癌细胞
生物物理学
材料科学
化学
免疫学
纳米技术
生物化学
生物
肿瘤细胞
纳米颗粒
氧气
内科学
体外
有机化学
操作系统
计算机科学
作者
Shasha He,Jing Li,Penghui Cheng,Ziling Zeng,Chi Zhang,Hongwei Duan,Kanyi Pu
标识
DOI:10.1002/ange.202106392
摘要
Abstract Nanomedicine can regulate the balance between cytotoxic T lymphocytes (CTLs) and suppressive regulatory T lymphocytes (Tregs), which however has been rarely exploited for cancer immunotherapy. We report a charge‐reversal polymer nano‐modulator (SP DMC N) activated by tumor microenvironment (TME) for photodynamic immunotherapy of cancer. SP DMC N is constructed by conjugating an immunomodulator (demethylcantharidin, DMC) to the side chains of a photodynamic polymer via an acid‐liable linker. The negative charge of SP DMC N ensures its high stability in blood circulation and ideal tumor accumulation; exposure to acidic TME reverses its surface charge to positive, enhancing tumor penetration and locally releasing DMC. Upon near‐infrared photoirradiation, SP DMC N generates singlet oxygen to ablate tumors and promote maturation of dendritic cells. Released DMC inhibits protein phosphatase 2 (PP2A) activity and decreases Tregs differentiation. Such combinational action induces a sharp increase in CTL/Treg ratio in TME and effectively inhibits both primary and distant tumors in living mice.
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