Single Atom-Doped Nanosonosensitizers for Mutually Optimized Sono/Chemo-Nanodynamic Therapy of Triple Negative Breast Cancer.
Single Atom-Doped Nanosonosensitizers for Mutually Optimized Sono/Chemo-Nanodynamic Therapy of Triple Negative Breast Cancer.
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DOI：
10.1002/advs.202206244
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发表时间：
2023-03
期刊：
影响因子：
15.1
通讯作者：
Jing, Xiangxiang
中科院分区：
文献类型：
--
作者：
Chen, Qiqing;Zhang, Min;Huang, Hui;Dong, Caihong;Dai, Xinyue;Feng, Guiying;Lin, Ling;Sun, Dandan;Yang, Dayan;Xie, Lin;Chen, Yu;Guo, Jia;Jing, Xiangxiang
关键词：
声动力疗法(SDT)是一种很有前途的治疗乳腺癌的方法，它依赖于产生丰富的活性氧自由基(ROS)来诱导氧化应激损伤。然而，突变乳腺癌，特别是三阴性乳腺癌(TNBC)，已经进化到获得特定的抗氧化防御功能，大大限制了SDT的杀伤力。在此，作者设计了一种独特的单一铜原子掺杂的二氧化钛纳米声敏剂，具有高度的催化和声敏活性，用于协同化学动力学和声动力学处理TNBC。单原子铜被固定在空心二氧化钛声敏剂最稳定的钛空位上，这不仅大大提高了铜介导的类芬顿反应的催化活性，而且通过促进电子(e−)和空穴(h+)的分离，大大提高了二氧化钛的声动力效率。体外和体内研究表明，工程化的单原子掺杂纳米声敏剂有效地实现了对TNBC的显著抑制作用，通过基于多功能单原子纳米声敏剂的声/化学-纳米动力学治疗的相互作用，为非侵入性、安全的肿瘤消除提供了一种治疗范式。开发了具有高度催化和声敏活性的铜/二氧化钛-聚乙二醇纳米声敏剂，用于三阴性乳腺癌的协同化疗和声动力学治疗。单原子掺铜不仅提高了铜介导类Fenton催化剂的催化活性，而且通过促进电子-空穴对的分离，提高了TiO2声动力学效率。该纳米系统为乳腺肿瘤的有效治疗提供了一种新的范式。
Sonodynamic therapy (SDT) represents a promising therapeutic modality for treating breast cancer, which relies on the generation of abundant reactive oxygen species (ROS) to induce oxidative stress damage. However, mutant breast cancers, especially triple‐negative breast cancer (TNBC), have evolved to acquire specific antioxidant defense functions, significantly limiting the killing efficiency of SDT. Herein, the authors have engineered a distinct single copper atom‐doped titanium dioxide (Cu/TiO2) nanosonosensitizer with highly catalytic and sonosensitive activities for synergistic chemodynamic and sonodynamic treatment of TNBC. The single‐atom Cu is anchored on the most stable Ti vacancies of hollow TiO2 sonosensitizers, which not only substantially improved the catalytic activity of Cu‐mediated Fenton‐like reaction, but also considerably augmented the sonodynamic efficiency of TiO2 by facilitating the separation of electrons (e−) and holes (h+). Both the in vitro and in vivo studies demonstrate that the engineered single atom‐doped nanosonosensitizers effectively achieved the significantly inhibitory effect of TNBC, providing a therapeutic paradigm for non‐invasive and safe tumor elimination through the mutual process of sono/chemo‐nanodynamic therapy based on multifunctional single‐atom nanosonosensitizers. The Cu/TiO2‐PEG nanosonosensitizer with highly catalytic and sonosensitive activities are developed for synergistic chemodynamic and sonodynamic treatment of triple‐negative breast cancer. The single‐atom Cu doping not only improved the Cu‐mediated Fenton‐like catalytic activity, but also augmented the sonodynamic efficiency of TiO2 by facilitating the separation of electron‐hole pairs. This nanosystem provided a novel paradigm for the effective treatment of breast tumors.
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