A Cascade Nanozyme with Amplified Sonodynamic Therapeutic Effects through Comodulation of Hypoxia and Immunosuppression against Cancer
A Cascade Nanozyme with Amplified Sonodynamic Therapeutic Effects through Comodulation of Hypoxia and Immunosuppression against Cancer
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级联纳米酶通过缺氧和免疫抑制的共同调节来增强声动力治疗效果以对抗癌症
DOI：
10.1021/acsnano.1c07504
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发表时间：
2021-12-28
期刊：
影响因子：
17.1
通讯作者：
Liu, You-Nian
中科院分区：
文献类型：
--
作者：
Tao, Na;Li, Huihuang;Liu, You-Nian
以免疫抑制和缺氧为特征的肿瘤微环境（TME）是肿瘤恶化和转移的关键。因此，调节TME以提高癌细胞消融效率在肿瘤治疗中受到广泛关注。然而，在TME中同时逆转免疫抑制和缓解缺氧是有效的癌症治疗的主要挑战。本文中，制备了基于Au纳米颗粒和具有内在级联酶模拟活性的碳点修饰的中空黑色TiO 2纳米球（HABT-C）的多功能平台，用于逆转TME中的免疫抑制和缓解缺氧。HABT-C纳米颗粒具有三酶模拟活性，可作为自级联纳米酶，产生足够的氧气以缓解缺氧并产生丰富的ROS。理论分析表明，黑色二氧化钛有利于吸收H2O和O-2，电子-空穴的分离，并产生活性氧，从而提高声动力学治疗（SDT）的效率。具体地，HABT-C表现出对免疫抑制介质表达的有利抑制，沿着免疫效应细胞浸润到TME中并逆转TME中的免疫抑制。因此，HABT-C可以通过引发免疫浸润、缓解缺氧和提高SDT效率来有效地杀死肿瘤细胞。这种基于级联纳米酶的平台（HABT-C@HA）将通过调节TME中的缺氧和免疫抑制来提供高效SDT抗癌的策略。
The tumor microenvironment (TME) featured by immunosuppression and hypoxia is pivotal to cancer deterioration and metastasis. Thus, regulating the TME to improve cancer cell ablation efficiency has received extensive interest in oncotherapy. However, to reverse the immunosuppression and alleviate hypoxia simultaneously in the TME are major challenges for effective cancer therapy. Herein, a multifunctional platform based on Au nanoparticles and a carbon dots modified hollow black TiO2 nanosphere (HABT-C) with intrinsic cascade enzyme mimetic activities is prepared for reversing immunosuppression and alleviating hypoxia in the TME. The HABT-C NPs possess triple-enzyme mimetic activity to act as self-cascade nanozymes, which produce sufficient oxygen to alleviate hypoxia and generate abundant ROS. The theoretical analysis demonstrates that black TiO2 facilitates absorption of H2O and O-2, separation of electron-holes, and generation of ROS, consequently amplifying the sonodynamic therapy (SDT) efficiency. Specifically, HABT-C exhibits favorable inhibition of immunosuppressive mediator expression, along with infiltrating of immune effector cells into the TME and reversing the immunosuppression in the TME. As a result, HABT-C can effectively kill tumor cells via eliciting immune infiltration, alleviating hypoxia, and improving SDT efficiency. This cascade nanozyme-based platform (HABT-C@HA) will provide a strategy for highly efficient SDT against cancer by modulation of hypoxia and immunosuppression in the TME.