声动力疗法
肿瘤微环境
癌症免疫疗法
化学
免疫原性细胞死亡
活性氧
癌症研究
癌症
免疫疗法
医学
肿瘤细胞
生物化学
内科学
作者
Xuan Tan,Jingzhao Huang,Yiqian Wang,Shasha He,Le Jia,Yanhong Zhu,Kanyi Pu,Yan Zhang,Xiangliang Yang
标识
DOI:10.1002/anie.202102703
摘要
Abstract Despite the promise of sonodynamic processes in cancer therapy, existing sonosensitizers often fail to regulate the generation of reactive oxygen species (ROS) against tumors, potentially leading to off‐target toxicity to normal tissues. We report a transformable core‐shell nanosonosensitizer (TiO 2 @CaP) that reinvigorates ROS generation and dissolves its CaP shell to release Ca 2+ in an acidic tumor microenvironment (TME) under ultrasound activation. Thus, TiO 2 @CaP acts as a smart nanosonosensitizer that specifically induces mitochondrial dysfunction via overloading intracellular Ca 2+ ions to synergize with the sonodynamic process in the TME. TiO 2 @CaP substantially enhances immunogenic cell death, resulting in enhanced T‐cell recruitment and infiltration into the immunogenic cold tumor (4T1). In conjunction with checkpoint blockade therapy (anti‐PD 1), TiO 2 @CaP‐mediated sonodynamic therapy elicits systemic antitumor immunity, leading to regression of non‐treated distant tumors and inhibition of lung metastasis. This work paves the way to development of “smart” TME‐activatable sonosensitizers with temporospatial control over antitumor responses.
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